SLK

protein-coding

STE20 like kinase

Gene summary

Enables protein homodimerization activity and protein serine/threonine kinase activity. Involved in several processes, including cytoplasmic microtubule organization; protein autophosphorylation; and regulation of focal adhesion assembly. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014720.4

Inheritance

ClinVar variants

P:1U:137B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr10:103,967,140-104,029,233

External References & Databases

Ensembl (ENSG00000065613)

Transcript & Mutation Effects

hg38 • Region Span ~62.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published PMID: 28940097 – Family 1 – one proband. Case-level (biallelic predicted null in AR model; homozygous; no consanguinity deduction applied) = 1.5; Segregation = 0; Case-control = 0 Family 1 total = 1.5 PMID: 40347834 – Family 2 – one proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 2 total = 1.0 PMID: 40347834 – Family 3 – one proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 3 total = 1.0 PMID: 40347834 – Family 4 – one proband. Case-level (AR compound heterozygous; non-LOF start = 1.0; variants evaluated independently then combined) = 0.2; Segregation = 0; Case-control = 0 Family 4 total = 0.2 Published genetic evidence total = 3.7 / 12 Genetic evidence – Our cases Family 1 – One proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Family 2 – One proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 2 total = 1.0 Total genetic evidence (published AR + our cases) 3.7 (published AR) + 2.0 (our cases) = 5.7 / 12 Experimental evidence – Published PMID: 40347834 – Functional studies demonstrate loss of SLK protein expression and cytoskeletal abnormalities in patient-derived and engineered cellular systems, supporting pathogenic loss-of-function. Functional alteration (patient-derived / engineered cellular assays; conservative) = 1.0 PMID: 40347834 – In vivo Drosophila Slik model demonstrates neuronal and locomotor defects consistent with SLK loss-of-function. Model system evidence (conservative) = 1.0 Gene function / biological plausibility (SLK role in cytoskeletal regulation and neuronal development) = 0.5 Experimental evidence total = 2.5 / 6 ________________________________________ Overall score Genetic evidence = 5.7 Experimental evidence = 2.5 Overall score = 8.2 / 18

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLK variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 131

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014720.4. 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			1 clinvar	1 clinvar		2
missense			131 clinvar	6 clinvar	1 clinvar	138
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	137	7	1	146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014720.4	RefSeq	NP_055535.2	19	MANE Select
ENST00000369755.4	Ensembl	ENSP00000358770.3	19	MANE Select
NM_001304743.2	RefSeq	NP_001291672.1	18	Standard
ENST00000335753.8	Ensembl	ENSP00000336824.4	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oocyte meiosis - Homo sapiens (human)
Caspase Cascade in Apoptosis

Biological Process

apoptotic process
signal transduction by protein phosphorylation
regulation of cell migration
stress-activated protein kinase signaling cascade
cytoplasmic microtubule organization

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding
identical protein binding
protein homodimerization activity

Cellular Component

cytoplasm
cell leading edge
perinuclear region of cytoplasm
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369755
Coding exons: 19
Length: 62033
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.65	442	629	0.703	0.0000318	8266
Missense (PolyPhen)		131	285.18	0.45935		3692
Synonymous	0.915	196	213	0.920	0.0000103	2146
Loss of Function	5.84	15	66.3	0.226	0.00000367	802

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000097	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.699
RVIS EVS: -0.37
RVIS percentile EVS: 28.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.590

Gene Damage Prediction

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