FETUB

protein-coding

fetuin B, the group of Cystatins, type 4

Gene summary

The protein encoded by this gene is a member of the fetuin family, part of the cystatin superfamily of cysteine protease inhibitors. Fetuins have been implicated in several diverse functions, including osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors, and response to systemic inflammation. This protein may be secreted by cells. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014375.3

Inheritance

—

ClinVar variants

U:60B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr3:186,635,969-186,653,141

External References & Databases

Ensembl (ENSG00000090512)

Transcript & Mutation Effects

hg38 • Region Span ~17.2 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 FETUB variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014375.3. 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 clinvar	4 clinvar	6
missense			58 clinvar	7 clinvar	2 clinvar	67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	60	8	6	74

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014375.3	RefSeq	NP_055190.2	7	MANE Select
ENST00000265029.8	Ensembl	ENSP00000265029.3	7	MANE Select
NM_001308077.4	RefSeq	NP_001295006.1	6	Standard
NM_001308079.4	RefSeq	NP_001295008.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

single fertilization
binding of sperm to zona pellucida
biological_process
negative regulation of endopeptidase activity

Molecular Function

molecular_function
cysteine-type endopeptidase inhibitor activity
metalloendopeptidase inhibitor activity

Cellular Component

extracellular region
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265029
Coding exons: 7
Length: 17173
Individuals with no LoFs: 125440
Homozygous LoFs: 2
Heterozygous LoFs: 306
Defined: 125748
p: 0.00123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.242	214	204	1.05	0.0000102	2448
Missense (PolyPhen)		67	62.192	1.0773		763
Synonymous	0.229	79	81.6	0.968	0.00000426	778
Loss of Function	0.537	12	14.2	0.846	7.50e-7	165

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0033	0.0033	notable
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0015	0.0015	notable
South Asian	0.00056	0.00056	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protease inhibitor required for egg fertilization. Required to prevent premature zona pellucida hardening before fertilization, probably by inhibiting the protease activity of ASTL, a protease that mediates the cleavage of ZP2 and triggers zona pellucida hardening (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.884
RVIS EVS: 0.62
RVIS percentile EVS: 83.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0579

Gene Damage Prediction

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