amelogenesis imperfecta, hypomaturation type, IIa6

disease

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Also known as AI2A6amelogenesis imperfecta, hypomaturation type, IIa6

Summary

amelogenesis imperfecta, hypomaturation type, IIa6 (MONDO:0014971) is a disease caused by GPR68 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: GPR68 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amelogenesis imperfecta, hypomaturation type, IIa6
Mondo ID	MONDO:0014971
OMIM	617217
DOID	DOID:0080960
UMLS	C4310665
MedGen	934632
GARD	0016211
Is cancer (heuristic)	no

Also known as: AI2A6 · amelogenesis imperfecta, hypomaturation type, IIa6 · amelogenesis imperfecta, hypomaturation type, IIa6; AI2A6

Data availability: 5 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 › amelogenesis imperfecta type 2 › amelogenesis imperfecta, hypomaturation type, IIa6

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
268084	NM_001177676.2(GPR68):c.386_835del (p.Phe129_Asn278del)	GPR68	Pathogenic	no assertion criteria provided
268085	NM_001177676.2(GPR68):c.667_668del (p.Lys223fs)	GPR68	Pathogenic	no assertion criteria provided
268086	NM_001177676.2(GPR68):c.221T>C (p.Leu74Pro)	GPR68	Pathogenic	no assertion criteria provided
728166	NM_001177676.2(GPR68):c.1006G>T (p.Glu336Ter)	GPR68	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805454	NM_001177676.2(GPR68):c.975dup (p.Glu326fs)	GPR68	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
GPR68	Strong	Autosomal recessive	amelogenesis imperfecta, hypomaturation type, IIa6	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GPR68	Orphanet:100033	Hypomaturation 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
GPR68	HGNC:4519	ENSG00000119714	Q15743	G-protein coupled receptor 68	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GPR68	G-protein coupled receptor 68	Proton-sensing G-protein coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPR68	GPCR	yes		GPCR_Rhodpsn, OGR1_rcpt, GPCR_Rhodpsn_7TM

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
gingival epithelium	1
granulocyte	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GPR68	203	broad	marker	tendon of biceps brachii, granulocyte, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPR68	923

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GPR68	Q15743	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class A/1 (Rhodopsin-like receptors)	1	74.2×	0.017	GPR68
G alpha (q) signalling events	1	57.4×	0.017	GPR68

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of osteoclast development	1	4213.0×	0.001	GPR68
negative regulation of monocyte differentiation	1	2407.4×	0.001	GPR68
osteoclast development	1	2106.5×	0.001	GPR68
cellular response to pH	1	2106.5×	0.001	GPR68
response to fluid shear stress	1	1872.4×	0.001	GPR68
monocyte differentiation	1	802.5×	0.003	GPR68
cellular response to acidic pH	1	732.7×	0.003	GPR68
insulin secretion	1	432.1×	0.004	GPR68
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	374.5×	0.004	GPR68
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.010	GPR68
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.010	GPR68
inflammatory response	1	37.7×	0.028	GPR68
G protein-coupled receptor signaling pathway	1	36.2×	0.028	GPR68

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GPR68	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GPR68	21	Functional:12, Binding:9

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	1	GPR68
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
GPR68	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: GPR68