PRRC2C

Chr 1

proline rich coiled-coil 2C

Also known as: BAT2-iso, BAT2D1, BAT2L2, XTP2

NCBI Gene: 23215 ENSG00000117523 UniProt: Q9Y520 OMIM: 617373

The PRRC2C protein binds RNA and is required for efficient formation of stress granules in the cytosol during cellular stress responses. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in stress granule assembly. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 10.19

OE 0.07 (0.04–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.49Z-score

OE missense 0.81 (0.77–0.85)

1155 obs / 1419.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.04–0.12)

0≤0.351.4

Missense OE?0.81 (0.77–0.85)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 10 / 140.1Missense obs/exp: 1155 / 1419.5Syn Z: -1.00

Background carrier burden — how many people carry a rare variant somewhere in PRRC2C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 20

3,330 rare PASS variants

Rare truncating (LoF)

1 in 680

155 rare PASS variants

Rare synonymous (reference)

1 in 37

1,370 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRRC2C. 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 24	1 in 800
South Asian	~43k	1 in 22	1 in 370
Remaining (unassigned)	~30k	1 in 18	1 in 750
European (Finnish)	~27k	1 in 41	1 in 960
Admixed American	~22k	1 in 19	1 in 210
African / African American	~21k	1 in 19	1 in 450
East Asian	~20k	1 in 24	1 in 2,400
Ashkenazi Jewish	~13k	1 in 94	1 in 820
Middle Eastern	~2,884	1 in 21	≈ 1 in 2,700

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): 29 of 34 coding exons well covered in gnomAD exomes; exons 2, 7, 17, 28, 34 marginal. Genomes: all 34.? see exons ↓