SRRM2

Chr 16AD

serine/arginine repetitive matrix 2

NCBI Gene: 23524ENSG00000167978UniProt: Q9UQ35

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)

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 72MIM #620439
AD
571
ClinVar variants
32
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SRRM2
⚡
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.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 424 VUS of 571 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-6.28Z-score
OE missense 1.43 (1.38–1.48)
2410 obs / 1684.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.04–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.43 (1.38–1.48)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.67
0≤1.21.6
LoF obs/exp: 7 / 111.4Missense obs/exp: 2410 / 1684.4Syn Z: -13.16

ClinVar Variant Classifications

571 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic14
VUS424
Likely Benign105
Benign5
Conflicting5
18
Pathogenic
14
Likely Pathogenic
424
VUS
105
Likely Benign
5
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
9
0
18
Likely Pathogenic
9
0
5
0
14
VUS
1
415
8
0
424
Likely Benign
0
77
6
22
105
Benign
0
3
0
2
5
Conflicting
—5
Total194952824571

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SRRM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SRRM2-related developmental disorder

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 72

MIM #620439

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder.
Cuinat S et al.·Genet Med
2022
Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations.
Liu D et al.·Nat Genet
2023
A Palindrome-Like Structure on 16p13.3 Is Associated with the Formation of Complex Structural Variations and SRRM2 Haploinsufficiency.
Pagnamenta AT et al.·Hum Mutat
2023
PRPF40A induces inclusion of exons in GC-rich regions important for human myeloid cell differentiation.
Tan CW et al.·Nucleic Acids Res
2024
Neurodevelopmental disorder and juvenile-onset tics associated with microdeletion of the SRRM2 gene.
Cavanna AE et al.·Neurol Sci
2025Case report
Retrospective identification of patients with SRRM2-related neurodevelopmental disorder in a single tertiary children's hospital.
Regan-Fendt KE et al.·Am J Med Genet A
2023Cohort
Familial and genetic association with neurodevelopmental disorders caused by a heterozygous variant in the SRRM2 gene.
Zhang T et al.·Front Endocrinol (Lausanne)
2023
SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection.
Guo J et al.·Clin Exp Med
2024
LINC00426 promotes the progression of atherosclerosis by regulating miR-873-5p/SRRM2 axis.
Zhou B et al.·Cytokine
2025
The intellectual disability gene PQBP1 rescues Alzheimer's disease pathology.
Tanaka H et al.·Mol Psychiatry
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools