ACVR1C / Activin receptor type-1C · IHC design guide

Design Immunohistochemistry for ACVR1C

Plan chromogenic ACVR1C IHC on paraffin sections with the catalog antibody's 1:100–1:300 dilution range (datasheet). Compare staining with the cytoplasmic tissue pattern while accounting for uncertain reliability and presumed off-target binding (HPA tissue IHC).

Evidence assembled Oct 2026 · For research use; verify linked source records and product datasheet before use
Immunohistochemistry protocol sheet for ACVR1C (IHC for ACVR1C): expected localisation Observed cytoplasmic staining (HPA tissue IHC); membrane localization (UniProt), antibody A30526, validated IHC image, and IHC protocol steps
Printable ACVR1C IHC protocol sheet — expected localisation Observed cytoplasmic staining (HPA tissue IHC); membrane localization (UniProt), antibody A30526, controls and protocol steps. Open the full ACVR1C IHC guide →

ACVR1C Immunohistochemistry Experimental Design Guide

Expected localisation, validated protocols, controls and antibodies — the at-a-glance facts below, then the full design guide.

Must know before staining
Expected localisation Observed cytoplasmic staining (HPA tissue IHC); membrane localization (UniProt)
Staining pattern Cytoplasmic staining in glandular cells across several tissues (HPA tissue IHC)
Antigen retrieval Citrate pH 6.0 HIER, 95–98 °C, 20 min (rule: cytoplasmic / membrane antigen)
Positive control ⓘ Adrenal gland+4 more · see all
Negative control ⓘ None in HPA (detected in all 45 tissues); use no-primary + isotype controls
Important caveats
Reasons your staining may differ from the expected pattern.
Fixation Keep fixation consistent across sections. (standard IHC practice; not target-specific)
Caveat Presumed off-target staining; reliability uncertain (HPA tissue IHC)
Regulation Placental expression throughout pregnancy (UniProt)
Isoform / epitope 4 isoforms; check epitope against extracellular and cytoplasmic regions (UniProt)
Section 1

Recommended ACVR1C IHC & IF Protocols

The catalog antibody’s IHC-P protocol is accompanied by a published ACVR1C protocol for colorectal cancer tissue (PMC13371181).

Recommended immunohistochemistry (IHC-P) protocol parameters
SampleParaffin-embedded human brain tissue; fixative not specified (datasheet A30526)
FixationImage fixative and duration unreported (datasheet A30526); verify before use.
Sectioning4–5 µm sections on charged slides (standard)
DeparaffinisationXylene, graded ethanol series to water (standard)
Antigen retrievalHeat-induced epitope retrieval in citrate buffer, pH 6.0, 20 min at 95–98 °C (standard rule: cytoplasmic / membrane antigen)
Peroxidase block3% H2O2, 10 min, room temperature (standard)
Blocking10% normal serum of the secondary host, 30 min, room temperature (standard)
Primary antibodyRabbit anti-ACVR1C, 1:100 - 1:300 (datasheet A30526)
Primary incubationOvernight at 4 °C (standard)
DetectionHRP-polymer secondary, DAB chromogen 5–10 min (standard)
CounterstainHematoxylin, blue, dehydrate and mount (standard)
Expected resultACVR1C-positive staining in glandular cells of adrenal gland (HPA tissue IHC: High). HPA tissue profile: General cytoplasmic expression in several different tissue types. No signal in the no-primary control.
💡Decision noteStart with citrate pH 6.0 retrieval at 95–98 °C for 20 min (page retrieval setting); ACVR1C is a membrane receptor (UniProt Q8NER5 topology).
Section 2

What Is the Expected ACVR1C Staining Pattern?

ACVR1C is a single-pass membrane receptor with an extracellular region and cytoplasmic kinase domain (UniProt Q8NER5 topology). In paraffin IHC, HPA reports general cytoplasmic staining across several tissues, including high staining in colon glandular cells, cerebral cortical neurons and lung macrophages (HPA tissue IHC). Interpret these observations cautiously: HPA rates tissue staining Uncertain because antibody staining and RNA expression show low consistency, and presumed off-target binding was disregarded (HPA reliability).

What am I looking at on my slide?
Cell-associated cytoplasmic or peripheral staining in colon glandular cells, cerebral cortical neurons, or lung macrophages.These cell types have High tissue IHC staining reported by HPA (HPA tissue IHC). A peripheral component fits the single-pass membrane topology (UniProt Q8NER5 topology), while cytoplasmic staining matches HPA's observed profile (HPA tissue IHC). Neither appearance alone establishes antibody specificity: both assessed HPA antibodies have Uncertain IHC validation (HPA antibodies HPA007982, HPA011933).
Predominantly nuclear staining, with little staining at the cell periphery or in the cytoplasm.A nuclear-dominant pattern conflicts with the membrane topology and HPA's general cytoplasmic tissue profile (UniProt Q8NER5 topology; HPA tissue IHC). Treat it as suspect and compare it with the counterstain and controls (general IHC practice). Cytoplasmic staining by itself cannot resolve the discrepancy between predicted membrane location and observed tissue IHC.
Strong staining in a different cell population while the HPA-reported cell population is faint.For example, strong lung epithelial staining with faint macrophages would differ from HPA's High macrophage observation (HPA tissue IHC). Consider cross-reactivity or endogenous chromogen activity, and check cell identity and detection controls (general IHC practice). HPA's Uncertain reliability makes an unexpected pattern a reason to validate, rather than immediate proof of either true expression or artefact (HPA reliability).
Uniform haze over tissue and spaces between cells, obscuring cell boundaries.This is difficult to score as cell-associated ACVR1C staining. Assess nonspecific binding, incomplete washing and endogenous detection activity with appropriate controls (general IHC practice). HPA describes cytoplasmic expression in several tissue types, but that observation does not validate diffuse slide-wide background (HPA tissue IHC).
No detectable staining in a section selected for an HPA-reported High cell population.First check tissue identity, the presence of the expected cells, antibody and detection performance, and the retrieval conditions (general IHC practice). Colon glandular cells and lung macrophages are reported High examples, but HPA assigns the tissue IHC evidence Uncertain reliability; an unstained section therefore needs technical review and independent biological interpretation (HPA tissue IHC; HPA reliability).
💡Expected ACVR1C appearanceFor paraffin IHC, the most plausible positive result is cell-associated cytoplasmic staining, possibly with a peripheral component, in an HPA-reported High population such as colon glandular cells or lung macrophages; dominant nuclear staining or diffuse cell-independent haze is suspect, and even a plausible pattern requires validation because HPA rates its tissue IHC Uncertain (HPA tissue IHC; HPA reliability; UniProt Q8NER5 topology).
How each factor affects the staining
Receptor topologyThe extracellular region spans residues 22–113, the transmembrane segment 114–134, and the cytoplasmic region 135–493 (UniProt Q8NER5 topology). This supports a membrane-associated expectation, but HPA tissue IHC reports a general cytoplasmic appearance (HPA tissue IHC).
Antibody validationBoth listed HPA antibodies, HPA007982 and HPA011933, have Uncertain IHC status; HPA reports low consistency between staining and RNA data and disregarded presumed off-target binding (HPA antibodies; HPA reliability). Use cell-specific controls before treating staining intensity as confirmed ACVR1C abundance (general IHC practice).
Choice of comparison tissueHPA reports High staining in several cell populations, including adrenal and breast glandular cells, kidney glomerular cells, and lung macrophages; it lists low staining in ovarian stroma and skin fibroblasts (HPA tissue IHC). Low is not an established absence, and no negative tissue is supplied (HPA tissue IHC).
Processing and epitopeUniProt lists a signal peptide at residues 1–20 and the mature chain at 21–493 (UniProt Q8NER5 processing). Antibody epitope location is not supplied, so the effect of processing on either listed antibody cannot be predicted.
IF/ICC: what location should be expected?A membrane-associated signal is consistent with UniProt topology and HPA's subcellular summary of Membrane (UniProt Q8NER5 topology; HPA subcellular). HPA supplies no ICC-IF image cell lines or main-location assignment, so this section cannot establish a cell-specific IF pattern (HPA subcellular).
Why is my staining missing, weak or wrong?
SituationLikely causeNext action
No signal in an HPA-reported High population.Missing expected cells, a detection failure, or retrieval conditions could explain the result (general IHC practice); HPA's High call is itself Uncertain (HPA tissue IHC; HPA reliability).Confirm the cell population and run appropriate positive and detection controls; review the antibody instructions and optimise retrieval as a general paraffin IHC step (general IHC practice).
Nuclear signal dominates.The compartment differs from UniProt's membrane topology and HPA's observed cytoplasmic profile (UniProt Q8NER5 topology; HPA tissue IHC).Check the counterstain and negative controls, then assess whether a second independently validated approach reproduces the cell-specific pattern (general IHC practice).
Strong signal appears mainly in an unexpected cell type.Cross-reactivity or endogenous detection activity is possible (general IHC practice), especially given HPA's Uncertain IHC validation (HPA reliability).Verify cell identity on the section; compare HPA-reported cell populations and use reagent and detection controls before scoring the signal (HPA tissue IHC; general IHC practice).
Diffuse brown haze masks cellular detail.Nonspecific reagent binding, inadequate washing, or endogenous peroxidase activity can produce background in chromogenic IHC (general IHC practice).Inspect reagent controls and review blocking, washing, antibody concentration and endogenous peroxidase control conditions (general IHC practice).
A low-staining comparison tissue is strongly positive.HPA lists ovarian stroma and skin fibroblasts as Low, not negative; unexpected intensity may also reflect nonspecific staining (HPA tissue IHC; general IHC practice).Check the cell population, staining distribution and controls; do not use a Low entry as an absolute negative standard (HPA tissue IHC; general IHC practice).
Only a sharp membrane rim stains, with little cytoplasmic signal.A rim is topology-consistent, but HPA describes general cytoplasmic tissue IHC and rates reliability Uncertain (UniProt Q8NER5 topology; HPA tissue IHC; HPA reliability).Record the compartment and cell type separately, then seek independent specificity evidence before calling the rim confirmed ACVR1C (general IHC practice).

Sample controls for ACVR1C IHC & IF

🧪Run cerebral cortex first and expect staining in neuronal cells (HPA: High in cerebral cortex neuronal cells). HPA detects ACVR1C in all 45 scored tissues, so use no-primary and isotype controls for the negative; non-neuronal cells on the same slide should show little background staining, but are not established ACVR1C-negative cells (HPA: no negative tissue rows; standard IHC practice).
Positive control tissue: Adrenal gland (Glandular cells, HPA High)
Negative control tissue: None in HPA: ACVR1C is detected in all 45 scored tissues. Use a no-primary (secondary-only) and an isotype control instead.
ICC-IF cell lines (HPA subcellular resource): HPA carries no ICC-IF cell line for ACVR1C; derive a cell-line control from the positive tissue's cell type (Glandular cells) and confirm it by RNA or western blot first.
Technical controls: Include a no-primary, secondary-only slide; use a host-species- and subclass-matched isotype for a monoclonal antibody, or species-matched nonimmune IgG for a polyclonal antibody; and compare with a peptide-blocked section (standard IHC practice; selected-SKU caption: staining blocked with synthesized peptide). Quench endogenous peroxidase for chromogenic detection and distinguish tissue pigment from chromogen in brain sections (standard IHC practice).
⚠️Feasibility: No target-specific fixation window or fixation effect is reported, and the selected-SKU paraffin-section caption does not state the fixative (selected-SKU caption). Antigen-retrieval dependence is unreported, so optimize retrieval empirically for the IHC-validated antibody; the supplied evidence does not establish whether frozen sections or IF are easier (selected-SKU caption; HPA: tissue staining only). In brain sections, tissue pigment can complicate chromogenic interpretation, so inspect the no-primary control alongside the stained section (standard IHC practice).

HPA tissue IHC evidence for ACVR1C

Comprehensive Human Protein Atlas IHC scoring per tissue (reliability: Uncertain — Low consistency between antibody staining and RNA expression data. Presumed off target binding observed and disregarded.). Rows are taken directly from the HPA tissue chart — click any row's HPA link to view the source.

Positive expression · recommended positive controls

TissueCell typeLevelEvidenceSource
Adrenal gland Glandular cells High Protein (IHC) HPA →
Breast Glandular cells High Protein (IHC) HPA →
Cerebral cortex Neuronal cells High Protein (IHC) HPA →
Colon Glandular cells High Protein (IHC) HPA →
Duodenum Glandular cells High Protein (IHC) HPA →

Undetected expression · recommended negative controls

TissueCell typeLevelEvidenceSource
None in HPA: ACVR1C is detected in all 45 scored tissues. Use a no-primary (secondary-only) and an isotype control instead.
Section 3

Advanced ACVR1C IHC Tips

Troubleshoot ACVR1C staining in paraffin sections by checking retrieval, cell context, membrane topology and the reliability of the observed pattern.

How should I retrieve ACVR1C in paraffin sections?
Use citrate buffer at pH 6.0 for heat-induced retrieval at 95–98 °C for 20 minutes (page retrieval specification). Let sections cool in buffer, then compare the test slide with a slide processed without primary antibody to assess detection background (standard IHC practice). ACVR1C has an extracellular region at residues 22–113 and a cytoplasmic region at 135–493, so record the antibody epitope before judging accessibility (UniProt Q8NER5 topology). If staining remains weak, adjust retrieval time in a small controlled series while keeping section thickness, detection and exposure to chromogen consistent (standard IHC practice).
Could fixation explain weak or uneven ACVR1C staining?
The supplied ACVR1C tissue-IHC caption identifies paraffin-embedded human brain but does not report its fixative, so target-specific fixation sensitivity is unknown (A30526 caption). Record fixative, fixation duration and processing history for each specimen before comparing stain intensity across samples (standard IHC practice). For a processing comparison, stain adjacent sections together with the same citrate pH 6.0, 95–98 °C, 20-minute retrieval and identical detection conditions (page retrieval specification; standard IHC practice). Review morphology and edge-to-center staining alongside the no-primary control; a difference between specimens alone cannot establish an ACVR1C-specific fixation effect (standard IHC practice).
What cellular pattern should I expect for ACVR1C?
ACVR1C is annotated as a membrane receptor with a transmembrane segment at residues 114–134 (UniProt Q8NER5 topology). Assess chromogenic staining at cell boundaries and in plausible intracellular receptor pools, while documenting the compartment actually seen rather than calling every diffuse signal membrane staining (UniProt Q8NER5 subcellular location; standard IHC practice). The HPA reports general cytoplasmic staining across tissues, but rates its tissue-IHC reliability uncertain because staining and RNA expression show low consistency and presumed off-target binding was observed (HPA tissue IHC). Compare cell-associated signal with no-primary and peptide-blocked controls before assigning a localisation to ACVR1C (A30526 caption; standard IHC practice).
How does epitope position affect interpretation across ACVR1C isoforms?
ACVR1C has 4 annotated isoforms, so establish which sequence the antibody recognises before interpreting staining as shared across isoforms (UniProt Q8NER5 isoforms; standard IHC practice). Map the immunogen to the extracellular residues 22–113, transmembrane residues 114–134 or cytoplasmic residues 135–493 when epitope information is available (UniProt Q8NER5 topology). The A30526 brain-section caption reports peptide blocking, which supports testing competition for that reagent but does not establish recognition of every isoform (A30526 caption; standard IHC interpretation). If the epitope is unspecified, report the result as staining with that antibody and avoid assigning an isoform from chromogenic appearance alone (standard IHC practice).
How can I check an IHC finding by multiplex IF?
Use IF as an orthogonal check of the IHC cell pattern, pairing ACVR1C with a marker of the cell population under study rather than treating color overlap alone as validation (standard IF practice). For lung sections, a macrophage marker is a relevant pairing because HPA reports high staining in lung macrophages, while its tissue-IHC reliability remains uncertain (HPA tissue IHC). Choose a fluorophore channel after inspecting tissue autofluorescence and include single-stain and no-primary controls to assess bleed-through and background (standard IF practice). Set permeabilisation according to whether the antibody targets the extracellular 22–113 or cytoplasmic 135–493 region, and verify accessibility empirically (UniProt Q8NER5 topology; standard IF practice).
How do I reduce diffuse brown staining without losing a plausible ACVR1C signal?
Compare a no-primary section with the test section after the same peroxidase block and DAB development to identify detection-related background (standard chromogenic IHC practice). Optimise antibody concentration, incubation and wash conditions in parallel sections, keeping citrate retrieval at pH 6.0, 95–98 °C for 20 minutes initially (page retrieval specification; standard IHC practice). Inspect pigment, tissue folds, cut edges and necrotic areas before counting brown deposits as cellular staining (standard IHC practice). General cytoplasmic ACVR1C staining in HPA should be interpreted cautiously because its tissue-IHC reliability is uncertain and presumed off-target binding was observed (HPA tissue IHC).
How should I score ACVR1C staining across sections? ⚠ ANSWER MARKED FOR VERIFICATION
Define the tissue compartment and eligible cells before scoring, then use an H-score based on staining intensity and percentage of positive cells for a comparable chromogenic series (standard IHC quantification practice). Alternatively, report percentage positive cells or positive-cell density per mm² when cell identification and area measurement are more reliable than intensity grading (standard IHC quantification practice). Normalise counts to the number of eligible cells or measured viable tissue area, and use the same threshold and imaging settings across sections (standard IHC quantification practice). Record membrane and cytoplasmic scores separately where distinguishable, and flag uncertain HPA tissue-IHC specificity when interpreting between-tissue differences (UniProt Q8NER5 subcellular location; HPA tissue IHC).
What would make an apparent ACVR1C-positive cell convincing?
Look for reproducible, cell-associated staining in an anatomically identified population, with a plausible membrane or intracellular receptor pattern and a clean no-primary control (UniProt Q8NER5 subcellular location; standard IHC practice). High HPA staining is reported in cerebral-cortex neuronal cells and lung macrophages, but HPA rates the tissue-IHC evidence uncertain, so those patterns are context rather than proof of specificity (HPA tissue IHC). Treat staining confined to section edges, necrosis, pigment or endogenous peroxidase-rich areas as suspect and check the corresponding control section (standard IHC practice). The A30526 brain image includes peptide blocking; use that observation as supporting evidence for its depicted stain, alongside independent controls and morphology (A30526 caption; standard IHC interpretation).
Boster reagents

Best ACVR1C / Activin receptor type-1C IHC Antibodies

The anti-ACVR1C catalog antibody has IHC data from paraffin-embedded human brain tissue and IF data from COS7 cells (A30526 image captions). Listed reactivity covers human, mouse, and rat (catalog reactivity).

Real IHC data Immunohistochemistry analysis of paraffin-embedded human brain tissue, using ACTR-1C Antibody. The picture on the right is blocked with the synthesized peptide.
Anti-ACTR-1C Antibody
Cat # A30526

A30526 is listed for IHC and IF/ICC, with IHC shown in paraffin-embedded human brain tissue and IF shown in COS7 cells (catalog applications; A30526 image captions). Both images include a peptide-blocked comparison (A30526 image captions).

Which to pick: Choose A30526 for paraffin-section tissue IHC; its own image shows human brain tissue, and the listed IHC dilution is 1:100–1:300 (A30526 IHC image caption; datasheet: IHC 1:100–1:300). For IF/ICC, A30526 is listed for both applications, with IF shown in COS7 cells and a listed ICC/IF dilution of 1:200–1:1000 (catalog applications; A30526 IF image caption; datasheet: ICC/IF 1:200–1:1000). For cross-species work, A30526 is a rabbit polyclonal listed as reactive with human, mouse, and rat; the fixative used for its paraffin-section IHC image is unreported (catalog host, clonality, and reactivity; A30526 IHC image caption).

Each figure is that product's own IHC / IF validation image from its datasheet.

References

  1. UniProt Consortium. UniProt entry Q8NER5 (ACV1C_HUMAN, Activin receptor type-1C).
  2. Human Protein Atlas. ACVR1C tissue IHC expression (reliability: Uncertain).
  3. Human Protein Atlas. ACVR1C subcellular location (ICC-IF): Membrane.
  4. Human Protein Atlas. ACVR1C antibody validation summary (2 antibodies).
  5. A paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C. Molecular cancer 2026 — PMC13371181.
  6. MEIS1‑regulated miR‑488‑3p suppresses the malignant progression of laryngeal squamous cell carcinoma by targeting ACVR1C. International journal of molecular medicine 2025 — PMC12270386.
  7. Integrated longitudinal analysis of adult grade 4 diffuse gliomas with long-term relapse interval revealed upregulation of TGF-β signaling in recurrent tumors. Neuro-oncology 2023 — PMC10076939.
  8. PubMed PMID:12063393 — UniProt-cited evidence.
  9. PubMed PMID:12606401 — UniProt-cited evidence.
  10. PubMed PMID:15815621 — UniProt-cited evidence.