HIVEP2

HIVEP zinc finger 2, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 6:142751468-142956698

Links

ENSG00000010818 ∙ NCBI:3097 ∙ OMIM:143054 ∙ HGNC:4921 ∙ Uniprot:P31629 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 43 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 43 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, autosomal dominant 43	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	23020937; 26153216; 27003583

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HIVEP2 gene.

• not provided (528 variants)
• Intellectual disability, autosomal dominant 43 (107 variants)
• Inborn genetic diseases (87 variants)
• not specified (23 variants)
• HIVEP2-related condition (10 variants)
• See cases (8 variants)
• Intellectual disability (5 variants)
• Angelman syndrome-like (2 variants)
• HIVEP2-Related Disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• Autism spectrum disorder (1 variants)
• HIVEP2-related syndromic intellectual disability (1 variants)
• Intellectual disability, autosomal dominant 13 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIVEP2 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	114	63	179
missense		3	261	145	24	433
nonsense	9	2				11
start loss						0
frameshift	17	8				25
inframe indel			7			7
splice donor/acceptor (+/-2bp)		2	1			3
splice region			4	2	2	8
non coding			2	2	2	6
Total	26	15	273	261	89

Variants in HIVEP2

This is a list of pathogenic ClinVar variants found in the HIVEP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-142753135-G-A			Likely benign (Sep 08, 2023)
6-142753138-T-G		Intellectual disability, autosomal dominant 43	Uncertain significance (Jan 18, 2024)
6-142753142-T-G			Uncertain significance (Nov 14, 2023)
6-142753143-GC-G			Uncertain significance (Sep 19, 2023)
6-142753149-C-T			Benign (Aug 22, 2022)
6-142753171-T-C			Uncertain significance (Aug 28, 2023)
6-142753178-T-C		HIVEP2-related disorder	Uncertain significance (Mar 23, 2023)
6-142753186-T-C			Uncertain significance (Apr 06, 2023)
6-142753225-G-A		Inborn genetic diseases	Likely benign (Dec 12, 2023)
6-142753232-G-A		Inborn genetic diseases	Likely benign (Dec 07, 2023)
6-142753236-T-C			Benign (Apr 13, 2023)
6-142753244-T-G			Likely benign (Oct 01, 2022)
6-142753275-A-G			Benign (Jun 07, 2023)
6-142753279-T-C			Uncertain significance (Feb 17, 2022)
6-142753280-G-T			Uncertain significance (Dec 19, 2023)
6-142753288-G-C		HIVEP2-related disorder	Uncertain significance (Jan 18, 2024)
6-142753290-G-T			Uncertain significance (Oct 01, 2019)
6-142753332-A-G			Benign (Apr 09, 2023)
6-142753343-T-C			Likely benign (Nov 18, 2023)
6-142753350-A-G			Benign (Jul 26, 2022)
6-142753351-T-C		Inborn genetic diseases	Likely benign (Oct 14, 2023)
6-142753352-G-A			Likely benign (Nov 11, 2022)
6-142753360-C-T		Inborn genetic diseases	Likely benign (Feb 06, 2024)
6-142753361-C-T		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)
6-142753376-G-A		Intellectual disability, autosomal dominant 43	Uncertain significance (Nov 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIVEP2	protein_coding	protein_coding	ENST00000367603	6	193735

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.60e-12	124789	0	7	124796	0.0000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	1129	1.32e+3	0.858	0.0000739	16010
Missense in Polyphen		317	516.63	0.61359		6391
Synonymous	-0.942	547	520	1.05	0.0000319	4889
Loss of Function	8.02	2	78.8	0.0254	0.00000432	1068

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000130	0.000129
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000354	0.0000353
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This protein specifically binds to the DNA sequence 5'- GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon- beta genes. It may act in T-cell activation.
• Disease: DISEASE: Mental retardation, autosomal dominant 43 (MRD43) [MIM:616977]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD43 patients manifest developmental delay, intellectual disability, hypotonia, and dysmorphic features. {ECO:0000269|PubMed:23020937, ECO:0000269|PubMed:26153216}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.0160
• rvis_EVS: -2.2
• rvis_percentile_EVS: 1.37

Haploinsufficiency Scores

• pHI: 0.579
• hipred: Y
• hipred_score: 0.825
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.852

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hivep2
• Phenotype: hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II
• Cellular component: nucleoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;metal ion binding