SRRM2

protein-coding

serine/arginine repetitive matrix 2, the group of Spliceosomal C complex|Spliceosomal P complex|NTC associated proteins

Gene summary

Enables C2H2 zinc finger domain binding activity. Involved in mRNA splicing, via spliceosome. Located in Cajal body and nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Implicated in autosomal dominant intellectual developmental disorder 72. Biomarker of Parkinson's disease. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_016333.4

Inheritance

ClinVar variants

P:79U:885B:273

Top phenotype

Intellectual developmental disorder, autosomal dominant 72

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr16:2,752,626-2,772,538

External References & Databases

Ensembl (ENSG00000167978)

Transcript & Mutation Effects

hg38 • Region Span ~19.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal dominant 72DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0957397

Submitter: Ambry Genetics

intellectual developmental disorder, autosomal dominant 72STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957397

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, autosomal dominant 72DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0957397

Submitter: G2P

intellectual developmental disorder, autosomal dominant 72STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957397

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal dominant 72AD

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 35567594; 37212523; 37272925

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRRM2 variants in ClinVar

11 Conditions Cataloged

Inborn genetic diseasesTotal: 756

not providedTotal: 367

not specifiedTotal: 118

Intellectual developmental disorder, autosomal dominant 72Total: 54

SRRM2-related disorderTotal: 46

Neurodevelopmental disorderTotal: 23

Status epilepticusTotal: 1

SRRM2-related Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016333.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	95 clinvar	6 clinvar	108
missense		1 clinvar	864 clinvar	160 clinvar	11 clinvar	1036
nonsense	23 clinvar	14 clinvar				37
start loss						0
frameshift	25 clinvar	14 clinvar	6 clinvar			45
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	8 clinvar	1 clinvar		11
Total	49	30	885	256	17	1237

Highest pathogenic variant AF is 0.0000065727204

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016333.4	RefSeq	NP_057417.3	14	MANE Select
ENST00000301740.13	Ensembl	ENSP00000301740.8	14	MANE Select
ENST00000570971.2	Ensembl	ENSP00000484503.1	8	Standard
ENST00000571378.5	Ensembl	ENSP00000458647.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

mRNA splicing, via spliceosome

Molecular Function

RNA binding
protein N-terminus binding
C2H2 zinc finger domain binding

Cellular Component

nucleus
nucleoplasm
Cajal body
nuclear speck
U2-type catalytic step 2 spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301740
Coding exons: 14
Length: 20210
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-6.28	2410	1.68e+3	1.43	0.000120	17102
Missense (PolyPhen)		276	238.17	1.1588		2512
Synonymous	-13.2	1030	615	1.67	0.0000360	6516
Loss of Function	9.16	7	111	0.0628	0.00000949	1060

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000065	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in pre-mRNA splicing. May function at or prior to the first catalytic step of splicing at the catalytic center of the spliceosome. May do so by stabilizing the catalytic center or the position of the RNA substrate (By similarity). Binds to RNA. {ECO:0000250, ECO:0000269|PubMed:10668804}.;

Recessive Scores

pRec: 0.235

Intolerance Scores

LoFtool: 0.174
RVIS EVS: -4.51
RVIS percentile EVS: 0.08

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.699

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium