SRPK3

protein-coding

SRSF protein kinase 3

Gene summary

This gene encodes a protein kinase similar to a protein kinase which is specific for the SR (serine/arginine-rich domain) family of splicing factors. A highly similar protein has been shown to play a role in muscle development in mice. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

Previous symbols:

STK23

MANE transcript

NM_014370.4

Inheritance

ClinVar variants

P:6U:152B:19

Top phenotype

Intellectual developmental disorder, X-linked 114

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chrX:153,776,412-153,785,732

External References & Databases

Ensembl (ENSG00000184343)

Transcript & Mutation Effects

hg38 • Region Span ~9.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

intellectual developmental disorder, X-linked 114LIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0975828

Submitter: Ambry Genetics

intellectual developmental disorder, X-linked 114STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0975828

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked 114XL

Manifestation: 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: 39073169

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRPK3 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 61

Intellectual developmental disorder, X-linked 114Total: 8

SRPK3-related disorderTotal: 2

Neurodevelopmental disorderTotal: 1

Congenital myopathyTotal: 1

Multiminicore myopathyTotal: 1

Autosomal recessive limb-girdle muscular dystrophy type 2JTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014370.4. 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			5 clinvar	9 clinvar	1 clinvar	15
missense	2 clinvar	1 clinvar	130 clinvar	8 clinvar	1 clinvar	142
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar	2 clinvar	3 clinvar			6
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	3	3	152	17	2	177

Highest pathogenic variant AF is 0.0000016626375

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014370.4	RefSeq	NP_055185.2	15	MANE Select
ENST00000370101.8	Ensembl	ENSP00000359119.3	15	MANE Select
NM_001170760.2	RefSeq	NP_001164231.1	15	Standard
NM_001170761.2	RefSeq	NP_001164232.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spliceosomal complex assembly
protein phosphorylation
skeletal muscle tissue development
regulation of gene expression
cell differentiation

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

cellular_component
nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370101
Coding exons: 15
Length: 9321
Individuals with no LoFs: 125557
Homozygous LoFs: 6
Heterozygous LoFs: 10
Defined: 125573
p: 0.0000637

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0307	262	263	0.995	0.0000242	3664
Missense (PolyPhen)		73	78.694	0.92764		1111
Synonymous	-3.23	164	119	1.38	0.0000117	1152
Loss of Function	3.26	5	21.2	0.235	0.00000151	346

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00041	0.00031	rare
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0.00014	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000050	0.000035	rare
South Asian	0.00011	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains. Phosphorylates the SR splicing factor SRSF1 and the lamin-B receptor (LBR) in vitro. Required for normal muscle development (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.652
RVIS EVS: -0.33
RVIS percentile EVS: 30.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.256

Gene Damage Prediction

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