RSRC1

Chr 3AR

arginine and serine rich coiled-coil 1

Also known as: BM-011, MRT70, SFRS21, SRrp53

NCBI Gene: 51319 ENSG00000174891 UniProt: Q96IZ7 OMIM: 613352

The protein regulates constitutive and alternative pre-mRNA splicing, including recognition of 3' splice sites during the second step of splicing. Mutations cause autosomal recessive intellectual developmental disorder. This gene shows tolerance to loss-of-function variants in the general population (low constraint), which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing. This gene may be associated with schizophrenia. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 70MIM #618402

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · complex neurodevelopmental disorder · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.84

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.12

OE 0.49 (0.30–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.87–1.11)

176 obs / 179.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.30–0.84)

0≤0.351.4

Missense OE?0.98 (0.87–1.11)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 10 / 20.3Missense obs/exp: 176 / 179.6Syn Z: -1.10

Background carrier burden — how many people carry a rare variant somewhere in RSRC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

420 rare PASS variants

Rare truncating (LoF)

1 in 1,500

84 rare PASS variants

Rare synonymous (reference)

1 in 510

157 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RSRC1. 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 180	1 in 1,700
South Asian	~43k	1 in 93	1 in 1,300
Remaining (unassigned)	~30k	1 in 100	1 in 1,900
European (Finnish)	~27k	1 in 330	1 in 730
Admixed American	~22k	1 in 120	1 in 3,400
African / African American	~21k	1 in 100	1 in 1,100
East Asian	~20k	1 in 200	1 in 1,400
Ashkenazi Jewish	~13k	1 in 520	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 89	none seen

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.