RHBDL1

protein-coding

rhomboid like 1, the group of Rhomboid family

Gene summary

This gene encodes a protein similar to Rhomboid in Drosophila which is involved in signalling in the Spitz/epidermal growth factor receptor/mitogen-activated protein kinase pathway. The Rhomboid family of proteins consists of intramembrane serine proteases containing several transmembrane domains. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

Previous symbols:

RHBDL

MANE transcript

NM_001278720.2

Inheritance

—

ClinVar variants

U:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr16:675,671-678,268

External References & Databases

Ensembl (ENSG00000103269)

Transcript & Mutation Effects

hg38 • Region Span ~2.6 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 RHBDL1 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001278720.2. 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			2 clinvar			2
missense			4 clinvar			4
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	6	0	0	6

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001278720.2	RefSeq	NP_001265649.1	8	MANE Select
ENST00000352681.8	Ensembl	ENSP00000344206.3	8	MANE Select
NM_001278721.2	RefSeq	NP_001265650.1	7	Standard
NM_001318733.2	RefSeq	NP_001305662.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

DroToll-like

Biological Process

proteolysis
signal transduction

Molecular Function

serine-type endopeptidase activity

Cellular Component

integral component of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219551
Coding exons: 7
Length: 2603
Individuals with no LoFs: 125192
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125201
p: 0.0000359

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	220	277	0.794	0.0000189	2776
Missense (PolyPhen)		92	143.99	0.63893		1404
Synonymous	-1.12	141	125	1.13	0.00000911	936
Loss of Function	2.95	4	17.2	0.232	7.39e-7	186

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000071	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000040	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. {ECO:0000250}.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.380
RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.221

Gene Damage Prediction

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