RHBDD1

rhomboid domain containing 1, the group of Rhomboid family

Basic information

Region (hg38): 2:226835581-226999215

Links

ENSG00000144468 ∙ NCBI:84236 ∙ OMIM:617515 ∙ HGNC:23081 ∙ Uniprot:Q8TEB9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RHBDD1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHBDD1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			15	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	1	1

Variants in RHBDD1

This is a list of pathogenic ClinVar variants found in the RHBDD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-226864700-C-T		not specified	Uncertain significance (Oct 12, 2021)
2-226864715-A-T		not specified	Uncertain significance (Apr 12, 2023)
2-226864719-A-G		not specified	Uncertain significance (Jul 21, 2021)
2-226864766-A-G		not specified	Uncertain significance (Sep 26, 2023)
2-226864823-A-T		not specified	Uncertain significance (May 27, 2022)
2-226864826-C-A		not specified	Uncertain significance (Apr 18, 2024)
2-226864845-G-A		not specified	Uncertain significance (Jun 11, 2021)
2-226864892-C-T		not specified	Uncertain significance (Nov 18, 2022)
2-226864893-G-A		not specified	Uncertain significance (Mar 28, 2024)
2-226864919-G-A		not specified	Uncertain significance (Mar 24, 2023)
2-226867264-C-G		not specified	Uncertain significance (Dec 21, 2023)
2-226867264-C-T		not specified	Uncertain significance (Jul 25, 2023)
2-226908871-T-A		not specified	Uncertain significance (Mar 30, 2024)
2-226914235-C-T		not specified	Uncertain significance (Jan 17, 2024)
2-226914283-C-T			Likely benign (Jan 01, 2023)
2-226914303-G-A		not specified	Uncertain significance (Jan 09, 2024)
2-226914315-C-T		not specified	Uncertain significance (Jun 29, 2023)
2-226914334-C-G		not specified	Uncertain significance (Jul 14, 2021)
2-226995455-C-A		not specified	Uncertain significance (May 07, 2024)
2-226995471-C-T			Benign (Oct 19, 2017)
2-226995484-A-G		not specified	Uncertain significance (Sep 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RHBDD1	protein_coding	protein_coding	ENST00000392062	6	163635

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.06e-12	0.0119	125712	1	30	125743	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0224	171	172	0.995	0.00000871	2052
Missense in Polyphen		37	50.273	0.73598		601
Synonymous	-0.495	70	64.9	1.08	0.00000358	595
Loss of Function	-0.577	17	14.6	1.16	6.16e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000165	0.000163
South Asian	0.000327	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Intramembrane-cleaving serine protease that cleaves single transmembrane or multi-pass membrane proteins in the hydrophobic plane of the membrane, luminal loops and juxtamembrane regions. Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded membrane proteins. Required for the degradation process of some specific misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Functions in BIK, MPZ, PKD1, PTCRA, RHO, STEAP3 and TRAC processing. Involved in the regulation of exosomal secretion; inhibits the TSAP6-mediated secretion pathway. Involved in the regulation of apoptosis; modulates BIK-mediated apoptotic activity. Also plays a role in the regulation of spermatogenesis; inhibits apoptotic activity in spermatogonia. {ECO:0000269|PubMed:18953687, ECO:0000269|PubMed:22624035}.

Recessive Scores

• pRec: 0.0635

Intolerance Scores

• loftool: 0.966
• rvis_EVS: 0.77
• rvis_percentile_EVS: 87.06

Haploinsufficiency Scores

• pHI: 0.0430
• hipred: N
• hipred_score: 0.167
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.436

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rhbdd1

Gene ontology

• Biological process: apoptotic process;positive regulation of protein processing;membrane protein intracellular domain proteolysis;cellular response to unfolded protein;cellular response to UV;ERAD pathway;negative regulation of apoptotic process;post-translational protein modification;spermatid differentiation;positive regulation of secretion;membrane protein proteolysis involved in retrograde protein transport, ER to cytosol;regulation of male germ cell proliferation
• Cellular component: mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane;endoplasmic reticulum quality control compartment
• Molecular function: endopeptidase activity;serine-type endopeptidase activity