ACVR1C

Chr 2

activin A receptor type 1C

Also known as: ACVRLK7, ALK7

NCBI Gene: 130399 ENSG00000123612 UniProt: Q8NER5 OMIM: 608981

ACVR1C is a type I receptor for the TGFB (see MIM 190180) family of signaling molecules. Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors (Bondestam et al., 2001 [PubMed 12063393]).[supplied by OMIM, Mar 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.001

Z-score 3.00

OE 0.37 (0.23–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.50Z-score

OE missense 0.74 (0.66–0.83)

198 obs / 266.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.23–0.63)

0≤0.351.4

Missense OE?0.74 (0.66–0.83)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 10 / 26.7Missense obs/exp: 198 / 266.9Syn Z: 0.07

Background carrier burden — how many people carry a rare variant somewhere in ACVR1C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

509 rare PASS variants

Rare truncating (LoF)

1 in 4,100

47 rare PASS variants

Rare synonymous (reference)

1 in 150

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACVR1C. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 3,400
South Asian	~43k	1 in 120	1 in 8,400
Remaining (unassigned)	~30k	1 in 150	1 in 3,800
European (Finnish)	~27k	1 in 310	1 in 2,700
Admixed American	~22k	1 in 160	1 in 4,500
African / African American	~21k	1 in 150	none seen
East Asian	~20k	1 in 220	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 470	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 9 coding exons well covered in gnomAD exomes; exons 8, 9 marginal. Genomes: all 9.? see exons ↓