SRRM2

Chr 16AD

serine/arginine repetitive matrix 2

ENSG00000167978 UniProt: Q9UQ35 OMIM: 606032

The protein is required for pre-mRNA splicing as a component of both major and minor spliceosomes, participating in the removal of introns from pre-mRNAs. Mutations cause intellectual developmental disorder, autosomal dominant 72, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function mutations (pLI ~1.0, LOEUF 0.118), indicating that functional copies are essential for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable)

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— SRRM2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 9.17

OE 0.06 (0.04–0.12)

Highly constrained

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

Missense Constraint?

-6.28Z-score

OE missense 1.43 (1.38–1.48)

2410 obs / 1684.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.06 (0.04–0.12)

0≤0.351.4

Missense OE?1.43 (1.38–1.48)

0≤0.61.4

Synonymous OE?1.67

0≤1.21.6

LoF obs/exp: 7 / 111.4Missense obs/exp: 2410 / 1684.4Syn Z: -13.16

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSRRM2-related developmental disorderLOFAD

This gene — mechanism propensity

0.2698th %ile

GOF

0.2696th %ile

LOF

0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.