RELT

protein-coding

RELT TNF receptor, the group of Tumor necrosis factor receptor superfamily|RELT family

Gene summary

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is especially abundant in hematologic tissues. It has been shown to activate the NF-kappaB pathway and selectively bind TNF receptor-associated factor 1 (TRAF1). This receptor is capable of stimulating T-cell proliferation in the presence of CD3 signaling, which suggests its regulatory role in immune response. Two alternatively spliced transcript variants of this gene encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

Previous symbols:

TNFRSF19L

MANE transcript

NM_152222.2

Inheritance

ClinVar variants

P:9U:76B:18

Top phenotype

Amelogenesis imperfecta, type IIIC

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr11:73,376,399-73,397,474

External References & Databases

Ensembl (ENSG00000054967)

Transcript & Mutation Effects

hg38 • Region Span ~21.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta, type 3CSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032717

Submitter: PanelApp Australia

amelogenesis imperfecta, type 3CSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032717

Submitter: Labcorp Genetics (formerly Invitae)

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta, type 3CMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032717

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IIICAR

Manifestation: Dental

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30506946

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RELT variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 72

RELT-related disorderTotal: 16

not providedTotal: 8

Amelogenesis imperfecta, type 3CTotal: 6

not specifiedTotal: 5

Amelogenesis imperfectaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152222.2. 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	4 clinvar	6
missense	2 clinvar	2 clinvar	71 clinvar	9 clinvar	3 clinvar	87
nonsense			1 clinvar			1
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	4 clinvar			7
Total	3	6	76	11	7	103

Highest pathogenic variant AF is 0.000033470813

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152222.2	RefSeq	NP_689408.1	10	MANE Select
ENST00000064780.7	Ensembl	ENSP00000064780.2	10	MANE Select
NM_001425248.1	RefSeq	NP_001412177.1	10	Standard
NM_001425249.1	RefSeq	NP_001412178.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine-cytokine receptor interaction - Homo sapiens (human)

Biological Process

apoptotic process

Molecular Function

protein binding

Cellular Component

nucleus
plasma membrane
integral component of membrane
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000064780
Coding exons: 10
Length: 21211
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125748
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.275	287	274	1.05	0.0000179	2714
Missense (PolyPhen)		95	99.433	0.95541		988
Synonymous	-0.675	124	115	1.08	0.00000770	933
Loss of Function	1.82	13	22.3	0.583	0.00000109	232

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0017	0.0017	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in apoptosis (PubMed:28688764, PubMed:19969290). Induces activation of MAPK14/p38 and MAPK8/JNK MAPK cascades, when overexpressed (PubMed:16530727). {ECO:0000269|PubMed:16530727, ECO:0000269|PubMed:19969290, ECO:0000269|PubMed:28688764}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.763
RVIS EVS: 0
RVIS percentile EVS: 54.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.302

Gene Damage Prediction

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