HIVEP1

protein-coding

HIVEP zinc finger 1, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes. [provided by RefSeq, Oct 2011]

Previous symbols:

ZNF40

MANE transcript

NM_002114.4

Inheritance

ClinVar variants

U:397B:79

Top phenotype

HIVEP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr6:12,008,762-12,164,999

External References & Databases

Ensembl (ENSG00000095951)

Transcript & Mutation Effects

hg38 • Region Span ~156.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published: PMID: 31130284 – Reports a heterozygous HIVEP1 variant (NM_002114.4:c.4111A>G; p.Ile1371Val). As autosomal recessive inheritance requires biallelic variants in trans, this case does not qualify for case-level scoring. Case-level = 0; segregation = 0; case-control = 0; PMID: 31130284 total = 0 Published genetic evidence total = 0/12 Genetic evidence – Our cases: Family 1 – one proband. Case-level (biallelic predicted null in AR model; homozygous scored once; −0.5 consanguinity deduction applied) = 1.0; segregation = 0; case-control = 0; Family 1 total = 1.0 Our cases total = 1.0/12 Total genetic evidence (published + our cases) 1.0/12 Experimental evidence – Published: There is no direct, published evidence yet that HIVEP1 variants cause neurodevelopmental disorders. However, its expression in neurons and related gene family members’ function in human NDD provide biological plausibility that HIVEP1 could impact neurodevelopment when disrupted. Experimental evidence total = 0/6 Overall score = 1.0

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HIVEP1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 410

not providedTotal: 46

HIVEP1-related disorderTotal: 19

Compulsive behaviorsTotal: 1

Myoepithelial tumorTotal: 1

SeizureTotal: 1

Attention deficit hyperactivity disorderTotal: 1

Hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002114.4. 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			4 clinvar	22 clinvar	6 clinvar	32
missense			389 clinvar	39 clinvar	12 clinvar	440
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	397	61	18	476

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002114.4	RefSeq	NP_002105.3	8	MANE Select
ENST00000379388.7	Ensembl	ENSP00000368698.2	8	MANE Select
ENST00000399469.3	Ensembl	ENSP00000382395.3	4	Standard
ENST00000442081.7	Ensembl	ENSP00000409078.3	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II distal enhancer sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein binding
metal ion binding

Cellular Component

nucleus
nucleoplasm
mitochondrion
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379388
Coding exons: 8
Length: 156238
Individuals with no LoFs: 124789
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 124808
p: 0.0000761

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.328	1409	1.44e+3	0.976	0.0000774	17710
Missense (PolyPhen)		338	464.48	0.7277		5735
Synonymous	-0.358	587	576	1.02	0.0000346	5545
Loss of Function	7.66	8	83.6	0.0957	0.00000463	1074

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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 HIV-1. 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, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis.;

Intolerance Scores

LoFtool: 0.339
RVIS EVS: 1.22
RVIS percentile EVS: 93.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.721

Gene Damage Prediction

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