amelogenesis imperfecta, type 3C

disease

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Also known as AI3C

Summary

amelogenesis imperfecta, type 3C (MONDO:0032717) is a disease caused by RELT (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: RELT (GenCC Strong)
Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amelogenesis imperfecta, type 3C
Mondo ID	MONDO:0032717
OMIM	618386
DOID	DOID:0111722
UMLS	C5193069
MedGen	1676410
GARD	0025728
Is cancer (heuristic)	no

Also known as: AI3C

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › amelogenesis imperfecta › hypocalcified amelogenesis imperfecta › amelogenesis imperfecta, type 3C

Related subtypes (2): amelogenesis imperfecta, type 3A, amelogenesis imperfecta type 3B

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
625368	NM_152222.2(RELT):c.1169_1170del (p.Pro390fs)	RELT	Pathogenic	no assertion criteria provided
625369	NM_152222.2(RELT):c.1265G>C (p.Arg422Pro)	RELT	Pathogenic	no assertion criteria provided
625370	NM_152222.2(RELT):c.121-2A>G	RELT	Pathogenic	no assertion criteria provided
694316	NM_152222.2(RELT):c.164C>T (p.Thr55Ile)	RELT	Pathogenic	no assertion criteria provided
3780543	NM_152222.2(RELT):c.862dup (p.Ala288fs)	RELT	Likely pathogenic	criteria provided, single submitter
694317	NM_152222.2(RELT):c.1264C>T (p.Arg422Trp)	RELT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RELT	Strong	Autosomal recessive	amelogenesis imperfecta, type 3C	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RELT	Orphanet:100032	Hypocalcified amelogenesis imperfecta

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RELT	HGNC:13764	ENSG00000054967	Q969Z4	Tumor necrosis factor receptor superfamily member 19L	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RELT	Tumor necrosis factor receptor superfamily member 19L	May play a role in apoptosis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RELT	Other/Unknown	no		TNF_rcpt_RELT, TNFR_19-like, TNFRSF19L_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RELT	191	ubiquitous	marker	monocyte, leukocyte, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RELT	1,180

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RELT	Q969Z4	63.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
amelogenesis	1	1404.3×	0.001	RELT
apoptotic process	1	28.7×	0.035	RELT

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RELT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RELT

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RELT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RELT