RHBDF2

rhomboid 5 homolog 2, the group of Rhomboid family

Basic information

Region (hg38): 17:76470891-76501790

Previous symbols: [ "RHBDL6", "TOC" ]

Links

ENSG00000129667NCBI:79651OMIM:614404HGNC:20788Uniprot:Q6PJF5AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • palmoplantar keratoderma-esophageal carcinoma syndrome (Strong), mode of inheritance: AD
  • palmoplantar keratoderma-esophageal carcinoma syndrome (Strong), mode of inheritance: AD
  • palmoplantar keratoderma-esophageal carcinoma syndrome (Supportive), mode of inheritance: AD
  • palmoplantar keratoderma-esophageal carcinoma syndrome (Moderate), mode of inheritance: AD
  • palmoplantar keratoderma-esophageal carcinoma syndrome (Definitive), mode of inheritance: AD
  • palmoplantar keratoderma-esophageal carcinoma syndrome (Definitive), mode of inheritance: AD
  • palmoplantar keratoderma-esophageal carcinoma syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Tylosis with esophageal cancerADOncologicSurveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Individuals may be at especially high risk of esophageal cancer with tobacco useDermatologic; Gastrointestinal; Oncologic13209063; 8508402; 8666405; 8651714; 22265016

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RHBDF2 gene.

  • Palmoplantar_keratoderma-esophageal_carcinoma_syndrome (216 variants)
  • not_provided (213 variants)
  • Inborn_genetic_diseases (118 variants)
  • RHBDF2-related_disorder (14 variants)
  • not_specified (6 variants)
  • Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHBDF2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001005498.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
51
clinvar
5
clinvar
64
missense
2
clinvar
239
clinvar
40
clinvar
3
clinvar
284
nonsense
0
start loss
0
frameshift
4
clinvar
4
splice donor/acceptor (+/-2bp)
0
Total 0 2 251 91 8

Highest pathogenic variant AF is 0.0000020665

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RHBDF2protein_codingprotein_codingENST00000313080 1730900
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.001190.9991257140321257460.000127
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.794325500.7850.00003715505
Missense in Polyphen148228.830.646762302
Synonymous0.7422152290.9380.00001571674
Loss of Function4.041340.90.3180.00000200430

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004830.000474
Ashkenazi Jewish0.0001030.0000992
East Asian0.00005440.0000544
Finnish0.0001430.000139
European (Non-Finnish)0.00007200.0000703
Middle Eastern0.00005440.0000544
South Asian0.0001640.000163
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Rhomboid protease-like protein which has no protease activity but regulates the secretion of several ligands of the epidermal growth factor receptor. Indirectly activates the epidermal growth factor receptor signaling pathway and may thereby regulate sleep, cell survival, proliferation and migration (By similarity). {ECO:0000250}.;

Recessive Scores

pRec
0.109

Intolerance Scores

loftool
0.756
rvis_EVS
-0.37
rvis_percentile_EVS
28.29

Haploinsufficiency Scores

pHI
0.228
hipred
Y
hipred_score
0.639
ghis
0.549

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.650

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rhbdf2
Phenotype
liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; cellular phenotype; skeleton phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
proteolysis;protein transport;regulation of epidermal growth factor receptor signaling pathway;regulation of protein secretion;negative regulation of protein secretion
Cellular component
endoplasmic reticulum membrane;plasma membrane;integral component of membrane
Molecular function
serine-type endopeptidase activity;growth factor binding