CISH

cytokine inducible SH2 containing protein, the group of Suppressors of cytokine signaling|SH2 domain containing

Basic information

Region (hg38): 3:50606489-50611774

Links

ENSG00000114737 ∙ NCBI:1154 ∙ OMIM:602441 ∙ HGNC:1984 ∙ Uniprot:Q9NSE2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CISH gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CISH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	14	4	1

Variants in CISH

This is a list of pathogenic ClinVar variants found in the CISH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-50607601-G-A		CISH-related disorder	Likely benign (Sep 17, 2019)
3-50607651-G-C		not specified	Uncertain significance (May 13, 2024)
3-50607663-G-T		not specified	Uncertain significance (Sep 29, 2023)
3-50607686-C-T			Uncertain significance (-)
3-50607715-C-T			Benign (Jun 14, 2018)
3-50607722-C-T		not specified	Uncertain significance (Oct 12, 2021)
3-50607734-C-T		not specified	Uncertain significance (Jun 10, 2022)
3-50607852-G-A		not specified	Uncertain significance (Jul 12, 2023)
3-50607855-C-T		not specified	Uncertain significance (Nov 11, 2024)
3-50607861-T-C		not specified	Uncertain significance (Aug 13, 2021)
3-50607865-G-A			Benign/Likely benign (Oct 01, 2022)
3-50607870-G-C		not specified	Uncertain significance (Aug 10, 2021)
3-50607939-G-A		not specified	Uncertain significance (Oct 06, 2024)
3-50607956-T-C		not specified	Uncertain significance (Apr 07, 2022)
3-50607968-C-T		not specified	Uncertain significance (Jan 03, 2024)
3-50607981-C-T		not specified	Uncertain significance (Jan 22, 2024)
3-50608381-C-T		CISH-related disorder	Likely benign (Mar 01, 2018)
3-50608476-C-T		CISH-related disorder	Likely benign (Jun 16, 2022)
3-50608528-A-G		not specified	Uncertain significance (Dec 13, 2023)
3-50608540-G-A		not specified	Uncertain significance (Oct 28, 2024)
3-50608567-C-T		not specified	Likely benign (Apr 08, 2024)
3-50608568-G-A		not specified	Uncertain significance (Feb 06, 2024)
3-50608588-C-G		not specified	Uncertain significance (May 26, 2024)
3-50610385-G-T		not specified	Uncertain significance (Dec 04, 2024)
3-50610395-C-T		not specified	Uncertain significance (Oct 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CISH	protein_coding	protein_coding	ENST00000443053	3	5342

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000539	0.714	125698	0	18	125716	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.889	147	181	0.814	0.0000117	1762
Missense in Polyphen		41	64.252	0.63811		628
Synonymous	0.800	63	71.6	0.880	0.00000431	599
Loss of Function	0.870	6	8.78	0.683	5.45e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000899	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.000101	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate- recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). {ECO:0000250}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);JAK-STAT-Ncore;Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;Leptin signaling pathway;Prolactin Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;JAK-STAT;IL-2 Signaling Pathway;EPO Receptor Signaling;Growth hormone receptor signaling;Prolactin;Cytokine Signaling in Immune system;Post-translational protein modification;Metabolism of proteins;Immune System;IL5-mediated signaling events;growth hormone signaling pathway;Neddylation;IL2-mediated signaling events;GMCSF-mediated signaling events;IL3-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.353
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.473
• hipred: Y
• hipred_score: 0.535
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cish
• Phenotype: hematopoietic system phenotype; respiratory system phenotype; immune system phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: cish
• Affected structure: myeloid cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: regulation of cell growth;protein kinase C-activating G protein-coupled receptor signaling pathway;protein ubiquitination;intracellular signal transduction;interleukin-7-mediated signaling pathway;regulation of phosphatidylinositol 3-kinase activity;post-translational protein modification;negative regulation of insulin receptor signaling pathway;phosphatidylinositol phosphorylation
• Cellular component: cellular_component;cytosol;plasma membrane;phosphatidylinositol 3-kinase complex
• Molecular function: molecular_function;protein binding;1-phosphatidylinositol-3-kinase regulator activity