CD96

CD96 molecule, the group of Immunoglobulin like domain containing|CD molecules|Ig-like cell adhesion molecule family

Basic information

Region (hg38): 3:111292718-111665750

Links

ENSG00000153283 ∙ NCBI:10225 ∙ OMIM:606037 ∙ HGNC:16892 ∙ Uniprot:P40200 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• C syndrome (Limited), mode of inheritance: AD
• C syndrome (Limited), mode of inheritance: AR
• C syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
C syndrome	AD	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	7258228; 3981579; 2260586; 10405439; 16835930; 16528754; 17847009

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD96 gene.

• not provided (49 variants)
• Inborn genetic diseases (28 variants)
• C syndrome (20 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD96 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				13	4	17
missense			30	4	3	37
nonsense			1			1
start loss			1			1
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			2		1	3
splice region				1	1	2
non coding			20	4	2	26
Total	0	0	56	21	10

Variants in CD96

This is a list of pathogenic ClinVar variants found in the CD96 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-111542250-T-C			Uncertain significance (Oct 17, 2023)
3-111542294-A-G			Uncertain significance (Dec 05, 2022)
3-111542298-A-AT		C syndrome	Conflicting classifications of pathogenicity (Apr 25, 2023)
3-111542326-T-C			Benign (Jan 12, 2024)
3-111545070-C-G		not specified	Uncertain significance (May 05, 2023)
3-111545115-C-T			Likely benign (Apr 24, 2023)
3-111545161-C-A			Likely benign (Aug 04, 2023)
3-111545161-C-T			Likely benign (Oct 17, 2018)
3-111545165-G-A			Uncertain significance (Nov 28, 2023)
3-111545183-C-A		not specified	Uncertain significance (Nov 13, 2023)
3-111545262-A-T			Uncertain significance (Dec 07, 2023)
3-111545313-G-A			Benign (Jun 01, 2022)
3-111545333-G-C		not specified	Uncertain significance (Aug 08, 2023)
3-111545343-T-C			Uncertain significance (May 17, 2021)
3-111545361-G-A		CD96-related disorder • not specified	Conflicting classifications of pathogenicity (Oct 25, 2023)
3-111545395-GAC-AAT			Uncertain significance (Sep 16, 2018)
3-111545409-A-G		CD96-related disorder	Likely benign (Apr 29, 2019)
3-111567526-C-A		not specified	Uncertain significance (Nov 09, 2021)
3-111567526-C-G			Uncertain significance (Oct 25, 2021)
3-111567528-G-C		CD96-related disorder	Benign (Jan 29, 2024)
3-111567553-C-T			Likely benign (Nov 19, 2022)
3-111567556-T-C		not specified	Uncertain significance (Nov 29, 2021)
3-111567588-C-T		not specified	Uncertain significance (Jun 29, 2022)
3-111567604-G-C			Uncertain significance (-)
3-111567609-T-C		C syndrome	Uncertain significance (Mar 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD96	protein_coding	protein_coding	ENST00000283285	15	373032

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-11	0.781	125225	6	516	125747	0.00208

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.467	329	306	1.08	0.0000149	3837
Missense in Polyphen		76	70.09	1.0843		930
Synonymous	-1.21	126	110	1.15	0.00000581	1105
Loss of Function	1.69	22	32.4	0.679	0.00000157	393

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0185	0.0183
Ashkenazi Jewish	0.000993	0.000993
East Asian	0.00642	0.00644
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.00642	0.00644
South Asian	0.000425	0.000425
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation.
• Disease: DISEASE: C syndrome (CSYN) [MIM:211750]: A syndrome characterized by trigonocephaly, severe mental retardation, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears. {ECO:0000269|PubMed:17847009}. Note=The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving CD96 has been found in a patient with C syndrome. Translocation t(3;18)(q13.13;q12.1). CD96 gene was located at the 3q13.13 breakpoint. Precise structural analysis around the breakpoint showed that the gene was disrupted by the translocation in exon 5, probably leading to premature termination or loss of expression of CD96 protein. No gene was detected at the chromosome 18 breakpoint.
• Pathway: Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System (Consensus)

Recessive Scores

• pRec: 0.0762

Intolerance Scores

• loftool: 0.980
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.19

Haploinsufficiency Scores

• pHI: 0.198
• hipred: N
• hipred_score: 0.169
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0357

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd96

Gene ontology

• Biological process: cytokine production involved in inflammatory response;negative regulation of natural killer cell cytokine production;immune response;cell adhesion;cell-matrix adhesion;response to lipopolysaccharide;negative regulation of interferon-gamma production;regulation of immune response
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;adherens junction