ZRANB1

protein-coding

zinc finger RANBP2-type containing 1, the group of OTU domain containing|Zinc fingers RANBP2-type

Gene summary

Enables K63-linked polyubiquitin modification-dependent protein binding activity and cysteine-type deubiquitinase activity. Involved in positive regulation of Wnt signaling pathway and protein deubiquitination. Located in cytosol and nucleoplasm. Is active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_017580.3

Inheritance

—

ClinVar variants

U:58B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr10:124,942,123-124,988,189

External References & Databases

Ensembl (ENSG00000019995)

Transcript & Mutation Effects

hg38 • Region Span ~46.1 kb

Loading mutation effect viewer...

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 ZRANB1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017580.3. 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	1
missense			58 clinvar	1 clinvar		59
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	58	1	1	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017580.3	RefSeq	NP_060050.2	9	MANE Select
ENST00000359653.4	Ensembl	ENSP00000352676.4	9	MANE Select
ENST00001141145.1	Ensembl	ENSP00000808768.1	9	Standard
XM_006717907.3	RefSeq	XP_006717970.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
zranb1b	Danio rerio	Structure: post-vent region Quality: curled abnormal

Gene / Model

Organism

Observed Phenotype

zranb1b

Danio rerio

Structure: post-vent region

Quality: curled

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Ovarian tumor domain proteases
Deubiquitination

Biological Process

cytoskeleton organization
Wnt signaling pathway
cell migration
protein deubiquitination
regulation of cell morphogenesis

Molecular Function

thiol-dependent ubiquitin-specific protease activity
protein binding
thiol-dependent ubiquitinyl hydrolase activity
metal ion binding
K63-linked polyubiquitin modification-dependent protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359653
Coding exons: 9
Length: 46067
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125741
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.08	222	394	0.564	0.0000216	4637
Missense (PolyPhen)		41	120.18	0.34115		1416
Synonymous	-0.757	145	134	1.08	0.00000679	1345
Loss of Function	5.05	4	37.3	0.107	0.00000205	416

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000098	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'- linked diubiquitin. Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones. Positive regulator of the Wnt signaling pathway that deubiquitinates APC protein, a negative regulator of Wnt-mediated transcription. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration. May also modulate TNF-alpha signaling. {ECO:0000269|PubMed:18281465, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22157957, ECO:0000269|PubMed:23827681}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.131
RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.719

Gene Damage Prediction

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