ZRANB3

protein-coding

zinc finger RANBP2-type containing 3, the group of Zinc fingers RANBP2-type

Gene summary

Enables ATP-dependent DNA/DNA annealing activity; DNA endonuclease activity; and K63-linked polyubiquitin modification-dependent protein binding activity. Involved in DNA repair; replication fork reversal; and response to UV. Located in nuclear replication fork and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032143.4

Inheritance

—

ClinVar variants

U:158B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr2:135,136,916-135,531,218

External References & Databases

Ensembl (ENSG00000121988)

Transcript & Mutation Effects

hg38 • Region Span ~394.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZRANB3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 145

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032143.4. 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			1 clinvar	3 clinvar	1 clinvar	5
missense			148 clinvar	7 clinvar	1 clinvar	156
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar		1 clinvar	8
Total	0	0	158	10	3	171

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032143.4	RefSeq	NP_115519.2	20	MANE Select
ENST00000264159.11	Ensembl	ENSP00000264159.6	20	MANE Select
NM_001286568.2	RefSeq	NP_001273497.1	20	Standard
NM_001286569.1	RefSeq	NP_001273498.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA strand renaturation
DNA repair
cellular response to DNA damage stimulus
response to UV
replication fork processing

Molecular Function

DNA helicase activity
endodeoxyribonuclease activity
protein binding
ATP binding
annealing helicase activity

Cellular Component

nucleus
nuclear replication fork

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264159
Coding exons: 20
Length: 394321
Individuals with no LoFs: 122467
Homozygous LoFs: 80
Heterozygous LoFs: 2092
Defined: 124639
p: 0.00875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.489	502	534	0.940	0.0000265	7075
Missense (PolyPhen)		158	179.58	0.87983		2503
Synonymous	0.563	179	189	0.948	0.00000983	1966
Loss of Function	1.87	40	55.0	0.727	0.00000289	698

Population LoF Frequency

Population	CAF	p-value	Status
African	0.11	0.11	notable
Latino/Admixed American	0.0067	0.0063	notable
Ashkenazi Jewish	0.0040	0.0037	notable
East Asian	0.00067	0.00067	rare
Finnish	0.00052	0.00051	rare
European (Non-Finnish)	0.0015	0.0015	notable
South Asian	0.0046	0.0043	notable
Other	0.0061	0.0058	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DNA annealing helicase and endonuclease required to maintain genome stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events (PubMed:21078962, PubMed:22704558, PubMed:22705370, PubMed:22759634, PubMed:26884333). Recruited to the sites of stalled DNA replication by polyubiquitinated PCNA and acts as a structure-specific endonuclease that cleaves the replication fork D-loop intermediate, generating an accessible 3'-OH group in the template of the leading strand, which is amenable to extension by DNA polymerase (PubMed:22759634). In addition to endonuclease activity, also catalyzes the fork regression via annealing helicase activity in order to prevent disintegration of the replication fork and the formation of double-strand breaks (PubMed:22705370, PubMed:22704558). {ECO:0000269|PubMed:21078962, ECO:0000269|PubMed:22704558, ECO:0000269|PubMed:22705370, ECO:0000269|PubMed:22759634, ECO:0000269|PubMed:26884333}.;

Intolerance Scores

RVIS EVS: 1.27
RVIS percentile EVS: 93.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.414

Gene Damage Prediction

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