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

Design Immunohistochemistry for ACVR1C

Plan chromogenic ACVR1C IHC in paraffin sections using the observed cytoplasmic tissue pattern and the receptor’s membrane topology (HPA tissue IHC; UniProt). Interpret staining cautiously because tissue IHC reliability is uncertain and presumed off-target binding has been observed (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 Cytoplasmic staining observed (HPA tissue IHC); membrane expected (UniProt), antibody A30526, validated IHC image, and IHC protocol steps
Printable ACVR1C IHC protocol sheet — expected localisation Cytoplasmic staining observed (HPA tissue IHC); membrane expected (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 Cytoplasmic staining observed (HPA tissue IHC); membrane expected (UniProt)
Staining pattern General cytoplasmic staining across several tissue types (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 Matched tissue-IHC evidence does not establish the fixation claim. Validate the specimen-specific method before use. (selected-SKU IHC image A30526)
Caveat Presumed off-target staining; tissue IHC reliability uncertain (HPA tissue IHC)
Regulation Expression varies by tissue (HPA tissue IHC)
Isoform / epitope 4 isoforms; check whether the epitope is extracellular or cytoplasmic (UniProt)
Section 1

Recommended ACVR1C IHC & IF Protocols

Compare the catalog antibody’s IHC-P protocol with one published ACVR1C IHC method in 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 HIER at 95–98 °C for 20 min (page antigen-retrieval rule); the published IHC method does not specify retrieval conditions (PMC13371181).
Section 2

What Is the Expected ACVR1C Staining Pattern?

ACVR1C is a single-pass membrane receptor with an extracellular region at residues 22–113 and a cytoplasmic region at 135–493 (UniProt Q8NER5 topology). In paraffin IHC, examine the HPA-reported glandular cells, neurons, glomerular cells and lung macrophages; HPA reports generally cytoplasmic staining, but rates its tissue IHC evidence Uncertain because staining and RNA data have low consistency and presumed off-target binding was observed (HPA: tissue IHC).

What am I looking at on my slide?
Membrane-associated staining in the expected cells, with possible cytoplasmic signal.Membrane association fits receptor topology (UniProt Q8NER5 topology). HPA describes general cytoplasmic staining but rates its IHC evidence Uncertain; confirm the pattern with controls before assigning either compartment specifically to ACVR1C (HPA: tissue IHC).
Predominantly nuclear staining, especially without a corresponding membrane-associated pattern.A nuclear-only pattern conflicts with the reported membrane location (UniProt Q8NER5 subcellular location; HPA: subcellular summary). Review morphology, background and controls before calling it positive.
Strong staining in cells outside the HPA-reported populations.Consider cross-reactivity or endogenous chromogenic activity. HPA observed presumed off-target binding, and its antibody IHC assessments are Uncertain (HPA: tissue IHC; HPA: HPA007982 and HPA011933 IHC). Cell identity alone cannot prove specificity.
Diffuse staining across tissue, including areas without a clear cellular pattern.This is difficult to score as receptor localisation; assess blocking, wash conditions and no-primary control as general IHC practice. HPA's uncertain tissue pattern gives no basis for treating uniform background as ACVR1C signal (HPA: tissue IHC).
No staining in a tissue with an HPA High cell population.First check whether that population is present and assess assay controls. HPA High is an observation, not a guaranteed positive for every antibody or section; HPA also reports low antibody-to-RNA consistency (HPA: tissue IHC).
💡Expected ACVR1C appearanceA credible positive is cell-associated staining, ideally with membrane association, in an HPA-reported High population such as lung macrophages or colon glandular cells; interpret intensity against local controls, because HPA also describes cytoplasmic staining and rates tissue IHC Uncertain, while isolated nuclear or uniform tissue-wide colour is suspect (UniProt Q8NER5 topology; HPA: tissue IHC).
How each factor affects the staining
Topology and compartmentACVR1C has one transmembrane segment at residues 114–134 (UniProt Q8NER5 topology). Membrane association is biologically plausible; the HPA cytoplasmic IHC profile needs independent confirmation because its reliability is Uncertain (HPA: tissue IHC).
Cell population used for comparisonHPA reports High staining in adrenal, breast, colon, duodenal and fallopian tube glandular cells; cerebral cortical neurons, glomerular cells and lung macrophages are also High (HPA: tissue IHC). Its Low examples are comparison points, not proven negatives (HPA: tissue IHC).
Antibody validationBoth listed rabbit polyclonal antibodies, HPA007982 and HPA011933, have Uncertain IHC assessments (HPA: antibodies). HPA reports presumed off-target binding; a plausible cell pattern therefore still needs appropriate specificity controls (HPA: tissue IHC).
Isoforms and epitope interpretationUniProt lists four ACVR1C isoforms and a signal peptide at residues 1–20, with the mature chain beginning at residue 21 (UniProt Q8NER5). The supplied record gives no antibody epitope, so isoform recognition or staining of the cleaved signal peptide cannot be inferred.
IF/ICC expectation?The separate IF/ICC guide should treat membrane staining as the location hypothesis (UniProt Q8NER5 subcellular location; HPA: subcellular summary). HPA supplies no ICC-IF image-bearing cell line or main-location assignment here, so an IF staining pattern is unconfirmed (HPA: subcellular).
Why is my staining missing, weak or wrong?
SituationLikely causeNext action
Only nuclei stain.The compartment conflicts with ACVR1C's reported membrane location (UniProt Q8NER5; HPA: subcellular summary).Compare no-primary and counterstain controls; recheck cellular boundaries and scoring before accepting a positive call (general IHC practice).
Colour appears in many unexpected cell types.Cross-reactivity is plausible because HPA reports presumed off-target binding; endogenous chromogenic activity can also contribute (HPA: tissue IHC; general IHC practice).Use a no-primary control and an appropriate endogenous-enzyme block, then compare staining with the reported cell populations (general IHC practice; HPA: tissue IHC).
Background obscures cell boundaries.Nonspecific reagent binding or incomplete washing can produce diffuse chromogen (general IHC practice).Review blocking, wash steps and detection-control slides; score only staining whose cellular distribution remains interpretable (general IHC practice).
An HPA High tissue gives no interpretable signal.The expected cell population may be absent from the section, or the assay may have failed; HPA High does not ensure this antibody will stain (HPA: tissue IHC).Verify the relevant cells on the counterstain and check assay controls; review the antibody's IHC-P conditions and retrieval workflow (general IHC practice).
Cytoplasmic staining dominates with little membrane detail.HPA reports general cytoplasmic IHC staining despite the membrane annotation, and calls the tissue result Uncertain (HPA: tissue IHC; HPA: subcellular summary).Record the distribution as observed, compare controls and seek independent specificity evidence before calling the cytoplasmic signal ACVR1C (general IHC practice; HPA: tissue IHC).
Different sections show inconsistent positive cells.HPA reports low consistency between antibody staining and RNA expression and rates both listed antibodies Uncertain for IHC (HPA: tissue IHC; HPA: antibodies).Check that the same cell populations are present, keep scoring criteria consistent and qualify conclusions that rely on a single staining pattern (general IHC practice).

Sample controls for ACVR1C IHC & IF

🧪Run cerebral cortex first and score neuronal cells, which HPA rates High for ACVR1C (HPA: High in cerebral cortex neuronal cells). HPA detects ACVR1C in all 45 scored tissues, so use no-primary and isotype controls in place of a negative tissue; neighboring cells should show counterstain without specific chromogen, but should not be assumed ACVR1C-negative (HPA: no negative tissue rows).
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 section, a species- and clonality-matched isotype control, and a biological specificity control using knockout material or peptide blocking; peptide blocking is shown for the selected brain IHC image (A30526 caption: peptide-blocked brain section). Quench endogenous peroxidase for chromogenic IHC and check whether neuronal lipofuscin pigment could be mistaken for chromogen (standard IHC practice).
⚠️Feasibility: A target-specific fixation window, fixation effect, and antigen retrieval dependency are unreported in the supplied evidence; the selected paraffin-section caption does not state a fixative (A30526 caption: fixative unreported). The evidence does not establish whether frozen sections or IF would be easier for ACVR1C. In cerebral cortex, neuronal lipofuscin can complicate interpretation of chromogenic staining (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, compartment, cell identity and controls before comparing staining intensity.

Which retrieval condition should I try first for weak ACVR1C staining?
Start with citrate buffer at pH 6.0, heated to 95–98 °C for 20 min (page retrieval setting). If staining remains weak, compare a second retrieval condition on adjacent sections while holding antibody concentration and detection constant (standard IHC practice). ACVR1C has an extracellular segment at residues 22–113 and a cytoplasmic segment at 135–493, so epitope location may affect accessibility (UniProt Q8NER5 topology). Include a section processed without primary antibody to identify retrieval-associated background (standard IHC practice). Record both signal and tissue preservation before choosing a condition (standard IHC practice).
How should I assess whether fixation explains inconsistent ACVR1C staining?
ACVR1C-specific sensitivity to fixation is unknown from the supplied evidence; the selected paraffin-section caption does not state a fixative (A30526 tissue-IHC caption). Record the fixative, fixation duration, section thickness and processing history for each specimen before comparing staining (standard IHC practice). Test sections with different known processing histories in the same run, using identical retrieval and detection conditions (standard IHC practice). Interpret weaker staining cautiously because differences in preservation or epitope accessibility can affect paraffin-section IHC (standard IHC practice). Do not use HPA tissue patterns to assign a fixation effect to ACVR1C (HPA: tissue-IHC reliability uncertain).
Where should convincing ACVR1C staining appear in paraffin sections?
Prioritise staining associated with cell membranes because ACVR1C is annotated as a membrane receptor with one transmembrane segment at residues 114–134 (UniProt Q8NER5 topology). Its extracellular region spans residues 22–113, while the cytoplasmic region spans 135–493 (UniProt Q8NER5 topology). A selected product image shows staining in paraffin-embedded human brain tissue with a peptide-blocked comparison, but does not establish a universal subcellular pattern (A30526 tissue-IHC caption). HPA reports general cytoplasmic tissue staining yet rates its IHC reliability uncertain (HPA: profile and reliability). Compare membrane-associated and diffuse cytoplasmic signal separately against controls (standard IHC practice).
Could ACVR1C isoforms or epitope position explain discordant staining?
ACVR1C has 4 annotated isoforms, so document which isoforms the antibody’s stated immunogen can recognise before interpreting discordant IHC (UniProt Q8NER5 isoforms; standard IHC practice). The supplied record places the extracellular region at residues 22–113 and the cytoplasmic region at 135–493 (UniProt Q8NER5 topology). It does not identify the selected antibody’s immunogen coordinates or establish isoform-specific staining (A30526 tissue-IHC caption). Compare staining from independent epitopes, if validated reagents are available, under matched section-processing conditions (standard IHC practice). Treat peptide blocking as support for competition with that peptide, not proof of isoform identity (A30526 tissue-IHC caption; standard IHC practice).
How can I extend the IHC findings into an ACVR1C multiplex IF experiment?
Treat IF as a separate validation experiment because the supplied product caption documents paraffin-section IHC, not IF performance (A30526 tissue-IHC caption). Pair ACVR1C with a marker identifying the cell population being evaluated, such as macrophages in lung sections where HPA reports high macrophage staining (HPA: High in lung macrophages). Choose spectrally separated fluorophores and reserve a bright channel for ACVR1C when tissue autofluorescence is substantial (standard IF practice). Match permeabilisation to the antibody epitope: a cytoplasmic epitope requires access across the membrane, while an extracellular epitope may be assessed without that step (UniProt Q8NER5 topology; standard IF practice). Include single-stain and no-primary controls (standard IF practice).
How do I troubleshoot widespread brown signal or tissue-edge staining?
First compare the section with a no-primary control and check whether signal concentrates at cut edges, damaged areas or pigment deposits (standard chromogenic IHC practice). Block endogenous peroxidase before enzyme-based detection and optimise protein blocking and wash conditions if nonspecific colour persists (standard chromogenic IHC practice). Titrate the IHC-validated antibody and chromogen development together, recording conditions that retain cellular contrast without diffuse background (standard chromogenic IHC practice). The peptide-blocked brain image provides a product-specific competition comparison, but its caption supplies no fixative or dilution (A30526 tissue-IHC caption). Be cautious with broad cytoplasmic staining because HPA reports presumed off-target binding and uncertain tissue-IHC reliability (HPA: reliability description).
How should I score ACVR1C IHC across specimens? ⚠ ANSWER MARKED FOR VERIFICATION
Define the cell compartment and population before scoring, then report the percentage of positive cells and an intensity-based H-score using the same thresholds across slides (standard IHC quantification practice). For spatial questions, count positive cells per mm² of viable tissue and state the sampled area (standard IHC quantification practice). Normalise to the number of evaluable cells or viable tissue area within the same annotated region, and keep staining batches and image settings comparable (standard IHC quantification practice). Score membrane-associated and cytoplasmic staining separately because ACVR1C is membrane annotated while HPA reports general cytoplasmic tissue expression (UniProt Q8NER5 subcellular; HPA: profile). Report controls and HPA’s uncertain reliability alongside comparisons (HPA: reliability).
What distinguishes credible ACVR1C positivity from an IHC artefact?
Give greatest weight to reproducible staining in the expected cell population with membrane association, consistent with ACVR1C’s membrane annotation (UniProt Q8NER5 subcellular; standard IHC practice). High HPA staining in lung macrophages or cerebral-cortex neuronal cells can guide cell-level review, but HPA rates its tissue-IHC reliability uncertain (HPA: positive cells and reliability). Check whether apparent positivity instead follows cut edges, necrotic regions, pigment or endogenous enzyme activity (standard chromogenic IHC practice). A peptide-blocked comparison is available for the selected paraffin-embedded human brain image, although competition alone does not establish target specificity (A30526 tissue-IHC caption; standard IHC practice). Resolve conflicting patterns with independent controls before making a biological claim (standard IHC practice).
Boster reagents

Best ACVR1C / Activin receptor type-1C IHC Antibodies

A30526 is listed for IHC and IF (catalog applications), with IHC data from paraffin-embedded human brain tissue (IHC image caption) and IF data from COS7 cells (IF image caption).

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 has an IHC image of paraffin-embedded human brain tissue (IHC image caption). The same SKU has an IF image of COS7 cells (IF image caption) and lists human, mouse and rat reactivity (catalog reactivity).

Which to pick: For tissue IHC, choose A30526: its IHC image shows paraffin-embedded human brain tissue (IHC image caption), and its listed IHC dilution is 1:100–1:300 (datasheet). For IF/ICC, A30526 lists both applications (catalog applications), has IF data from COS7 cells (IF image caption), and lists an ICC/IF dilution of 1:200–1:1000 (datasheet). For cross-species work, A30526 is a rabbit polyclonal listed as reactive with human, mouse and rat (catalog host, clonality and reactivity); its IHC caption supports paraffin sections, but does not report the fixative (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.