RHBDD2

protein-coding

rhomboid domain containing 2, the group of Rhomboid family

Gene summary

The protein encoded by this gene is a member of the rhomboid family of membrane-bound proteases and is overexpressed in some breast cancers. Members of this family are involved in intramembrane proteolysis. In mouse, the orthologous protein associates with the Golgi body. [provided by RefSeq, Sep 2016]

Previous symbols:

RHBDL7

MANE transcript

NM_001040456.3

Inheritance

—

ClinVar variants

U:75B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr7:75,842,602-75,888,926

External References & Databases

Ensembl (ENSG00000005486)

Transcript & Mutation Effects

hg38 • Region Span ~46.3 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 RHBDD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040456.3. 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		2
missense			72 clinvar	1 clinvar		73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	75	2	0	77

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040456.3	RefSeq	NP_001035546.1	4	MANE Select
ENST00000006777.11	Ensembl	ENSP00000006777.6	4	MANE Select
NM_001040457.3	RefSeq	NP_001035547.1	3	Standard
NM_001346186.2	RefSeq	NP_001333115.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity

Cellular Component

Golgi membrane
nucleus
nucleoplasm
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000006777
Coding exons: 4
Length: 46325
Individuals with no LoFs: 124808
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124813
p: 0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.665	183	210	0.871	0.0000127	2281
Missense (PolyPhen)		58	71.628	0.80973		731
Synonymous	0.724	91	100	0.908	0.00000678	832
Loss of Function	2.66	2	11.9	0.168	5.94e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.0462
RVIS EVS: -0.49
RVIS percentile EVS: 22.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.433

Gene Damage Prediction

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