HHLA2

HERV-H LTR-associating 2, the group of V-set domain containing|C1-set domain containing|B7 family

Basic information

Region (hg38): 3:108296529-108378285

Links

ENSG00000114455 ∙ NCBI:11148 ∙ OMIM:604371 ∙ HGNC:4905 ∙ Uniprot:Q9UM44 ∙ 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 HHLA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HHLA2 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						0
missense			34	3		37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	34	3	0

Variants in HHLA2

This is a list of pathogenic ClinVar variants found in the HHLA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-108351830-C-T		not specified	Likely benign (Nov 26, 2024)
3-108351844-C-G		not specified	Uncertain significance (Jul 12, 2022)
3-108351844-C-T		not specified	Likely benign (Oct 24, 2024)
3-108353440-G-T		not specified	Uncertain significance (Mar 08, 2024)
3-108353477-G-A		not specified	Likely benign (Aug 10, 2021)
3-108353481-T-C		not specified	Uncertain significance (Sep 27, 2024)
3-108353510-C-T		not specified	Uncertain significance (Sep 30, 2024)
3-108353634-G-T		not specified	Uncertain significance (May 23, 2023)
3-108355139-A-G		not specified	Uncertain significance (Nov 22, 2024)
3-108355178-T-C		not specified	Uncertain significance (Dec 05, 2022)
3-108355183-A-G		not specified	Uncertain significance (Jan 26, 2022)
3-108355193-C-T		not specified	Uncertain significance (Sep 27, 2021)
3-108355195-C-T		not specified	Uncertain significance (Sep 30, 2024)
3-108355248-G-A		not specified	Uncertain significance (Oct 25, 2022)
3-108355258-G-C		not specified	Uncertain significance (Jul 14, 2021)
3-108355282-A-G		not specified	Uncertain significance (Jan 22, 2024)
3-108355304-G-A		not specified	Uncertain significance (Jan 08, 2024)
3-108355331-T-C		not specified	Uncertain significance (Sep 13, 2023)
3-108355337-A-T		not specified	Uncertain significance (Dec 16, 2023)
3-108355366-C-T		not specified	Uncertain significance (Oct 04, 2022)
3-108355373-C-T		not specified	Uncertain significance (Oct 12, 2021)
3-108357855-A-G		not specified	Uncertain significance (May 31, 2023)
3-108357860-G-T		not specified	Uncertain significance (Mar 15, 2024)
3-108357873-G-A		not specified	Uncertain significance (Sep 12, 2023)
3-108357897-A-C		not specified	Uncertain significance (Aug 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HHLA2	protein_coding	protein_coding	ENST00000357759	8	81757

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000173	0.877	124564	0	21	124585	0.0000843

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.573	194	218	0.891	0.0000111	2720
Missense in Polyphen		25	31.888	0.784		394
Synonymous	1.77	62	82.4	0.752	0.00000479	757
Loss of Function	1.55	12	19.3	0.621	9.06e-7	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000651	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.000730	0.000724
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000177
Middle Eastern	0.000730	0.000724
South Asian	0.000179	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade. {ECO:0000269|PubMed:23784006}.

Recessive Scores

• pRec: 0.0708

Intolerance Scores

• loftool: 0.844
• rvis_EVS: 1.82
• rvis_percentile_EVS: 96.99

Haploinsufficiency Scores

• pHI: 0.0472
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.283

Gene Damage Prediction

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

Gene ontology

• Biological process: positive regulation of cytokine production;T cell costimulation;positive regulation of activated T cell proliferation;regulation of immune response;T cell receptor signaling pathway
• Cellular component: cellular_component;external side of plasma membrane;integral component of membrane
• Molecular function: molecular_function;signaling receptor binding;protein binding