CLNK

protein-coding

cytokine dependent hematopoietic cell linker, the group of SH2 domain containing

Gene summary

MIST is a member of the SLP76 family of adaptors (see LCP2, MIM 601603; BLNK, MIM 604515). MIST plays a role in the regulation of immunoreceptor signaling, including PLC-gamma (PLCG1; MIM 172420)-mediated B cell antigen receptor (BCR) signaling and FC-epsilon R1 (see FCER1A, MIM 147140)-mediated mast cell degranulation (Cao et al., 1999 [PubMed 10562326]; Goitsuka et al., 2000, 2001 [PubMed 10744659] [PubMed 11463797]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_052964.4

Inheritance

—

ClinVar variants

U:78B:14

Top phenotype

CLNK-related disorder

gnomAD constraint

pLI —, LoF o/e 1.36

Max pathogenic AF

—

Genomic locus

chr4:10,486,395-10,684,768

External References & Databases

Ensembl (ENSG00000109684)

Transcript & Mutation Effects

hg38 • Region Span ~198.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLNK variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 3

CLNK-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052964.4. 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				2 clinvar		2
missense			72 clinvar	12 clinvar		84
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	78	14	0	92

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052964.4	RefSeq	NP_443196.2	18	MANE Select
ENST00000226951.11	Ensembl	ENSP00000226951.6	18	MANE Select
ENST00000507719.1	Ensembl	ENSP00000427208.1	9	Standard
ENST00000515667.5	Ensembl	ENSP00000427256.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

immune response
transmembrane receptor protein tyrosine kinase signaling pathway
positive regulation of signal transduction
intracellular signal transduction

Molecular Function

SH3/SH2 adaptor activity
protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000226951
Coding exons: 18
Length: 198471
Individuals with no LoFs: 124540
Homozygous LoFs: 0
Heterozygous LoFs: 104
Defined: 124644
p: 0.000417

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.560	243	220	1.11	0.0000113	2810
Missense (PolyPhen)		65	57.902	1.1226		698
Synonymous	-0.964	88	77.2	1.14	0.00000425	730
Loss of Function	-1.76	38	27.9	1.36	0.00000126	364

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0011	notable
Latino/Admixed American	0.00025	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0011	0.0011	notable
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00051	0.00049	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation. Involved in phosphorylation of LAT (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.558
RVIS EVS: 0.69
RVIS percentile EVS: 85.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.267

Gene Damage Prediction

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