WDR72

Summary

WDR72 (WD repeat domain 72, HGNC:26790) is a protein-coding gene on chromosome 15q21.3, encoding WD repeat-containing protein 72 (Q3MJ13). Plays a major role in formation of tooth enamel.

This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 256764 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelogenesis imperfecta (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 55
• Clinical variants (ClinVar): 509 total — 12 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 4
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_182758

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26790
Approved symbol	WDR72
Name	WD repeat domain 72
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38736
Ensembl gene	ENSG00000166415
Ensembl biotype	protein_coding
OMIM	613214
Entrez	256764

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000360509, ENST00000396328, ENST00000557913, ENST00000559418, ENST00000560036, ENST00000567224, ENST00000567575, ENST00000864447, ENST00000864448, ENST00000864449, ENST00000864450, ENST00000929049, ENST00000953083, ENST00000953084, ENST00000953085, ENST00000953086, ENST00000953087

RefSeq mRNA: 2 — MANE Select: NM_182758 NM_001277176, NM_182758

CCDS: CCDS10151

Canonical transcript exons

ENST00000360509 — 20 exons

Exon	Start	End
ENSE00001102747	53711336	53711481
ENSE00001102749	53704988	53705233
ENSE00001102755	53712772	53712891
ENSE00001102762	53705927	53706074
ENSE00001102770	53710857	53710953
ENSE00001278430	53665572	53665768
ENSE00001278436	53699750	53699945
ENSE00001278443	53702134	53702354
ENSE00001278459	53714434	53714510
ENSE00001278502	53715193	53715367
ENSE00001278509	53716607	53716685
ENSE00001278514	53722802	53722908
ENSE00001278961	53615426	53616243
ENSE00001334675	53597079	53597274
ENSE00001334677	53609513	53609592
ENSE00001334679	53613666	53613757
ENSE00001383635	53732997	53733161
ENSE00001524592	53759633	53759663
ENSE00003659562	53523218	53523322
ENSE00003678593	53513741	53517754

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 99.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3813 / max 106.1350, expressed in 91 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150057	0.3756	91
150056	0.0058	2

Top tissues by expression

227 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.80	gold quality
pancreatic ductal cell	CL:0002079	96.89	gold quality
renal medulla	UBERON:0000362	96.76	gold quality
parotid gland	UBERON:0001831	94.05	gold quality
adult mammalian kidney	UBERON:0000082	93.91	gold quality
epithelial cell of pancreas	CL:0000083	93.06	gold quality
kidney	UBERON:0002113	92.50	gold quality
thyroid gland	UBERON:0002046	89.78	gold quality
liver	UBERON:0002107	89.06	gold quality
right lobe of thyroid gland	UBERON:0001119	88.95	gold quality
left lobe of thyroid gland	UBERON:0001120	88.81	gold quality
right lobe of liver	UBERON:0001114	87.67	gold quality
metanephros cortex	UBERON:0010533	86.61	gold quality
cortex of kidney	UBERON:0001225	86.37	gold quality
upper leg skin	UBERON:0004262	85.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.44	gold quality
caput epididymis	UBERON:0004358	81.33	gold quality
metanephros	UBERON:0000081	81.16	gold quality
adult organism	UBERON:0007023	81.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.52	gold quality
secondary oocyte	CL:0000655	79.14	gold quality
palpebral conjunctiva	UBERON:0001812	78.82	gold quality
skin of hip	UBERON:0001554	77.75	gold quality
decidua	UBERON:0002450	77.14	gold quality
duodenum	UBERON:0002114	75.71	gold quality
saliva-secreting gland	UBERON:0001044	75.50	gold quality
buccal mucosa cell	CL:0002336	75.33	silver quality
oocyte	CL:0000023	74.47	gold quality
tibia	UBERON:0000979	74.03	gold quality
jejunal mucosa	UBERON:0000399	72.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	5420.85
E-CURD-119	yes	28.36
E-CURD-135	no	681.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting WDR72, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• investigation of autosomal-recessive hypomaturation amelogenesis imperfecta (AI) in a consanguineous Pakistani family; a locus on chromosome 15q21.3 was identified; sequencing revealed a point mutation in the WDR72 gene (PMID:19853237)
• A novel WDR72 dinucleotide deletion mutation (g.57,426_57,427delAT; c.1467_ 1468delAT; p.V491fsX497) was identified in both alleles of probands from Mexico and Turkey. WDR72 is a cytoplasmic protein that is critical for dental enamel formation. (PMID:20938048)
• Hypomaturation amelogenesis imperfecta due to WDR72 mutations: a novel mutation and ultrastructural analyses of deciduous teeth (PMID:21196691)
• the 4 recently reported SNPs,located near BNC2, SORCS1, GSC and WDR72 loci, affecting glycemic control in type 1 diabetes had no apparent effect on HbA1c in type 2 diabetes; but, for SORCS1 SNP, findings do not rule out possible relationship with HbA1c (PMID:21294870)
• The rs11056571, p=1.68x10(-8); and rs2300290, p=1.09x10(-8)). rs719714 downstream of WDR72 was associated with executive functioning. (PMID:22126837)
• WDR72 has a major role in enamel mineralization, most notably during the maturation stage, suggesting a function involving endocytic vesicle trafficking, and the removal of amelogenin proteins. (PMID:25008349)
• Based on whole exome sequencing in a large consanguineous amelogenesis imperfecta pedigree, an evidence for presence of a multi-exonic WDR72 deletion has been obtained. (PMID:27259663)
• WDR72 mutations associated with dRTA have not been previously described. This is the first identification of pathogenic variations in WDR72 as a cause of hereditary dRTA. (PMID:30028003)
• WDR72 mutations cause a syndromic form of AI and improve our ability to diagnose AI caused by WDR72 defects (PMID:30779877)
• Identification of the C-terminal region in Amelogenesis Imperfecta causative protein WDR72 required for Golgi localization. (PMID:35301423)
• Long non-coding RNA X-Inactive Specific Transcript (XIST) interacting with USF2 promotes osteogenic differentiation of periodontal ligament stem cells through regulation of WDR72 transcription. (PMID:37712743)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wdr72	ENSMUSG00000044976
rattus_norvegicus	Wdr72	ENSRNOG00000054889

Paralogs (2): RBBP5 (ENSG00000117222), VPS8 (ENSG00000156931)

Protein

Protein identifiers

WD repeat-containing protein 72 — Q3MJ13 (reviewed: Q3MJ13)

All UniProt accessions (4): Q3MJ13, H0YKE0, H0YLX4, H0YN02

UniProt curated annotations — full annotation on UniProt →

Function. Plays a major role in formation of tooth enamel. Specifically required during the maturation phase of amelogenesis for normal formation of the enamel matrix and clearance of enamel proteins. May be involved in localization of the calcium transporter SLC24A4 to the ameloblast cell membrane.

Subcellular location. Cytoplasmic vesicle.

Disease relevance. Amelogenesis imperfecta, hypomaturation type, 2A3 (AI2A3) [MIM:613211] A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_877435* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR049916	WDR72-like	Family
IPR057848	WDR72_alpha-sol	Domain

Pfam: PF00400, PF23123

UniProt features (21 total): repeat 8, sequence variant 6, sequence conflict 4, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3MJ13-F1	67.22	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 1083, 1081

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): RORA1_01, TGACCTY_ERR1_Q2, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_LOCALIZATION_WITHIN_MEMBRANE, TGACCTTG_SF1_Q6, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, NUYTTEN_NIPP1_TARGETS_DN, VECCHI_GASTRIC_CANCER_EARLY_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, GOBP_PROTEIN_LOCALIZATION_TO_PLASMA_MEMBRANE, ERR1_Q2, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP

GO Biological Process (2): biomineral tissue development (GO:0031214), protein localization to plasma membrane (GO:0072659)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue development	1
animal organ development	1
protein localization to membrane	1
protein localization to cell periphery	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR72	MMP20	O60882	968
WDR72	KLK4	Q9Y5K2	862
WDR72	SACK1H	Q6ZRV2	828
WDR72	ODAPH	Q17RF5	813
WDR72	ENAM	Q9NRM1	788
WDR72	AMELX	Q99217	753
WDR72	AMBN	Q9NP70	714
WDR72	FAM20A	Q96MK3	709
WDR72	LAMB3	Q13751	708
WDR72	SLC24A4	Q8NFF2	690
WDR72	AMTN	Q6UX39	660
WDR72	MMP25	Q9NPA2	583
WDR72	ACP4	Q9BZG2	539
WDR72	COL17A1	Q9UMD9	525
WDR72	GPR68	Q15743	523

IntAct

4 interactions, top by confidence:

A	B	Type	Score
	DENND11	psi-mi:“MI:0914”(association)	0.350
WDR72	DNAJB5	psi-mi:“MI:0914”(association)	0.350
nadA	WDR72	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): WDR72 (Affinity Capture-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS), WDR72 (Proximity Label-MS)

ESM2 similar proteins: A1L3L1, A2RT67, A3KPW7, A4IIA7, A8C750, A8C752, D2HNY3, E1BGQ2, E1C3P4, Q08CL8, Q08DZ8, Q0IHB3, Q149N8, Q1RMU2, Q1RMZ1, Q3MJ13, Q3T1H6, Q5F3F2, Q5RED8, Q5VVJ2, Q5ZJ87, Q66J91, Q69Z66, Q6AYF5, Q6DE97, Q6GR37, Q6P1E7, Q6PNC0, Q6YHU6, Q7TPQ3, Q8BKW4, Q8BXK4, Q8IWR0, Q8IYF3, Q8IZE3, Q8K2I9, Q8NA31, Q8NEN0, Q8NFZ0, Q96EW2

Diamond homologs: D3YYM4, Q3MJ13, Q5RFQ4, Q920I9, Q9ERH3, Q9Y4E6, Q26544

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

509 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	33
Uncertain significance	347
Likely benign	36
Benign	40

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
161415	NM_182758.4(WDR72):c.1467_1468del (p.Val491fs)	Pathogenic
1879841	NM_182758.4(WDR72):c.2680_2699delinsACTATAGTT (p.Ser894fs)	Pathogenic
1879842	NM_182758.4(WDR72):c.1766-2423_1962+1074del	Pathogenic
1895441	NM_182758.4(WDR72):c.2332dup (p.Met778fs)	Pathogenic
1895442	NM_182758.4(WDR72):c.1287_1289del (p.Ile430del)	Pathogenic
231	NM_182758.4(WDR72):c.2348C>G (p.Ser783Ter)	Pathogenic
232	NM_182758.4(WDR72):c.2934G>A (p.Trp978Ter)	Pathogenic
233	NM_182758.4(WDR72):c.2857del (p.Ser953fs)	Pathogenic
3577445	NM_182758.4(WDR72):c.997A>T (p.Lys333Ter)	Pathogenic
521052	NM_182758.4(WDR72):c.708G>A (p.Trp236Ter)	Pathogenic
522609	NM_182758.4(WDR72):c.2522T>A (p.Leu841Gln)	Pathogenic
688610	GRCh37/hg19 15q21.3(chr15:53871541-53993518)x1	Pathogenic
1344707	NM_182758.4(WDR72):c.477_485dup (p.Ile159_Cys161dup)	Likely pathogenic
2445427	NM_182758.4:c.-13+989_7del	Likely pathogenic
2445444	NM_182758.4(WDR72):c.118C>T (p.Gln40Ter)	Likely pathogenic
2445445	NM_182758.4(WDR72):c.954+1_954+10del	Likely pathogenic
2445448	NM_182758.4(WDR72):c.2146del (p.Ala716fs)	Likely pathogenic
2445449	NM_182758.4(WDR72):c.2388del (p.Lys796fs)	Likely pathogenic
2504595	NM_182758.4(WDR72):c.2864T>G (p.Leu955Ter)	Likely pathogenic
3064917	NM_182758.4(WDR72):c.858-1G>C	Likely pathogenic
3065340	NM_182758.4(WDR72):c.1348+1G>T	Likely pathogenic
3076032	NM_182758.4(WDR72):c.2019dup (p.Trp674fs)	Likely pathogenic
3350517	NM_182758.4(WDR72):c.1347del (p.Asp450fs)	Likely pathogenic
3382480	NM_182758.4(WDR72):c.2555del (p.Gly852fs)	Likely pathogenic
3577376	NM_182758.4(WDR72):c.2871_2872+7del	Likely pathogenic
3577395	NM_182758.4(WDR72):c.2473C>T (p.Gln825Ter)	Likely pathogenic
3577398	NM_182758.4(WDR72):c.2383_2385delinsCC (p.Ala795fs)	Likely pathogenic
3577405	NM_182758.4(WDR72):c.2127dup (p.Gly710fs)	Likely pathogenic
3577409	NM_182758.4(WDR72):c.2078T>A (p.Leu693Ter)	Likely pathogenic
3577416	NM_182758.4(WDR72):c.1862C>G (p.Ser621Ter)	Likely pathogenic

SpliceAI

4885 predictions. Top by Δscore:

Variant	Effect	Δscore
15:53523318:TGGAG:T	acceptor_gain	1.0000
15:53523323:C:CA	acceptor_loss	1.0000
15:53523323:C:CC	acceptor_gain	1.0000
15:53523326:T:TC	acceptor_gain	1.0000
15:53597077:A:AC	donor_gain	1.0000
15:53597078:C:CA	donor_gain	1.0000
15:53597078:CT:C	donor_gain	1.0000
15:53597078:CTTTG:C	donor_gain	1.0000
15:53597273:ACCT:A	acceptor_loss	1.0000
15:53597275:C:CA	acceptor_loss	1.0000
15:53638259:C:CT	donor_gain	1.0000
15:53665769:C:CC	acceptor_gain	1.0000
15:53699941:CTTAG:C	acceptor_gain	1.0000
15:53699943:TAG:T	acceptor_gain	1.0000
15:53699946:C:CC	acceptor_gain	1.0000
15:53702132:A:AC	donor_gain	1.0000
15:53702133:C:CC	donor_gain	1.0000
15:53705008:T:TA	donor_gain	1.0000
15:53705169:TTGTG:T	donor_gain	1.0000
15:53705191:T:C	donor_gain	1.0000
15:53705923:TTAC:T	donor_loss	1.0000
15:53705924:TACC:T	donor_loss	1.0000
15:53705926:C:CA	donor_loss	1.0000
15:53705926:CCT:C	donor_gain	1.0000
15:53708205:C:T	acceptor_gain	1.0000
15:53710950:CCCA:C	acceptor_gain	1.0000
15:53710951:CCA:C	acceptor_gain	1.0000
15:53710951:CCAC:C	acceptor_gain	1.0000
15:53710952:CA:C	acceptor_gain	1.0000
15:53710952:CAC:C	acceptor_gain	1.0000

AlphaMissense

7260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:53722816:A:C	S82R	0.999
15:53722816:A:T	S82R	0.999
15:53722818:T:G	S82R	0.999
15:53733020:A:G	W44R	0.998
15:53733020:A:T	W44R	0.998
15:53722820:A:T	V81D	0.997
15:53699765:A:G	W584R	0.996
15:53699765:A:T	W584R	0.996
15:53714466:A:G	W187R	0.996
15:53714466:A:T	W187R	0.996
15:53715327:A:G	L127P	0.996
15:53716672:A:G	W92R	0.996
15:53716672:A:T	W92R	0.996
15:53714501:A:G	L175P	0.994
15:53699763:C:A	W584C	0.993
15:53699763:C:G	W584C	0.993
15:53712777:A:G	W236R	0.993
15:53712777:A:T	W236R	0.993
15:53712800:A:G	L228P	0.993
15:53733018:C:A	W44C	0.993
15:53733018:C:G	W44C	0.993
15:53609533:A:G	W978R	0.992
15:53609533:A:T	W978R	0.992
15:53712822:A:G	C221R	0.992
15:53733042:A:C	S36R	0.992
15:53733042:A:T	S36R	0.992
15:53733044:T:G	S36R	0.992
15:53705975:A:G	W352R	0.991
15:53705975:A:T	W352R	0.991
15:53715322:A:G	C129R	0.991

dbSNP variants (sampled 300 via entrez): RS1000034246 (15:53558688 G>A), RS1000040373 (15:53613096 C>G,T), RS1000042549 (15:53638347 A>G), RS1000046626 (15:53719869 C>T), RS1000053664 (15:53652224 T>A), RS1000061706 (15:53580715 T>G), RS1000067816 (15:53753239 T>C), RS1000072600 (15:53644254 T>A), RS1000075146 (15:53703315 C>T), RS1000076261 (15:53567095 A>C,T), RS1000103637 (15:53675326 A>C), RS1000104164 (15:53527073 A>G), RS1000109560 (15:53599269 G>C), RS1000111611 (15:53513493 A>G), RS1000114559 (15:53643187 T>C,G)

Disease associations

OMIM: gene MIM:613214 | disease phenotypes: MIM:613211, MIM:104500, MIM:611590

GenCC curated gene-disease

Disease	Classification	Inheritance
amelogenesis imperfecta hypomaturation type 2A3	Strong	Autosomal recessive
amelogenesis imperfecta type 2	Supportive	Autosomal recessive
renal tubular acidosis	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amelogenesis imperfecta	Definitive	AR

Mondo (7): amelogenesis imperfecta hypomaturation type 2A3 (MONDO:0013181), distal renal tubular acidosis (MONDO:0015827), hypophosphatemic rickets (MONDO:0024300), amelogenesis imperfecta (MONDO:0019507), renal tubular acidosis, distal, 4, with hemolytic anemia (MONDO:0012700), renal tubular acidosis (MONDO:0001909), amelogenesis imperfecta type 2 (MONDO:0015048)

Orphanet (3): Amelogenesis imperfecta (Orphanet:88661), Distal renal tubular acidosis (Orphanet:18), Distal renal tubular acidosis with anemia (Orphanet:93610)

HPO phenotypes

4 total (5 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000705	Amelogenesis imperfecta
HP:0006285	Enamel hypomineralization
HP:0011085	Hypomature dental enamel
HP:0008341	Distal renal tubular acidosis

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST000583_8	Hematological and biochemical traits	2.000000e-08
GCST000649_27	Chronic kidney disease	3.000000e-13
GCST000785_27	Longevity	1.000000e-06
GCST001332_2	Cognitive function	4.000000e-08
GCST001606_7	Renal function-related traits (sCR)	1.000000e-13
GCST001607_6	Renal function-related traits (eGRFcrea)	6.000000e-13
GCST001610_4	Renal function-related traits (BUN)	3.000000e-11
GCST002935_25	Lead levels	9.000000e-06
GCST003372_54	Glomerular filtration rate (creatinine)	3.000000e-15
GCST003401_4	Glomerular filtration rate in non diabetics (creatinine)	1.000000e-12
GCST003790_17	Glomerular filtration rate	2.000000e-11
GCST003790_3	Glomerular filtration rate	3.000000e-08
GCST003790_4	Glomerular filtration rate	7.000000e-07
GCST003831_25	Asthma	1.000000e-06
GCST004292_7	Glomerular filtration rate (creatinine)	7.000000e-11
GCST005984_38	Glomerular filtration rate	5.000000e-37
GCST005985_55	Creatinine levels	3.000000e-34
GCST005986_40	Blood urea nitrogen levels	2.000000e-30
GCST006030_14	Chloride levels	3.000000e-17
GCST006031_11	Potassium levels	3.000000e-12
GCST006032_11	Sodium levels	2.000000e-10
GCST006976_82	Macular thickness	2.000000e-09
GCST007344_101	Estimated glomerular filtration rate	7.000000e-07
GCST007344_136	Estimated glomerular filtration rate	3.000000e-36
GCST007344_50	Estimated glomerular filtration rate	8.000000e-42
GCST007576_255	Chronotype	5.000000e-11
GCST007876_34	Estimated glomerular filtration rate	1.000000e-39
GCST007916_23	Hyperuricemia	2.000000e-16
GCST007917_10	Estimated glomerular filtration rate	2.000000e-16
GCST007918_12	Serum uric acid levels	2.000000e-16

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004323	mental process
EFO:0009283	potassium measurement
EFO:0009282	sodium measurement
EFO:0008328	chronotype measurement
EFO:0009104	hyperuricemia
EFO:0004761	uric acid measurement
EFO:0010136	urinary pH measurement
EFO:0005670	smoking initiation
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement
EFO:0004458	C-reactive protein measurement
EFO:0600008	mitochondrial heteroplasmy measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000141	Acidosis, Renal Tubular	C12.050.351.968.419.815.093; C12.200.777.419.815.093; C12.950.419.815.093; C16.320.831.093; C18.452.076.176.210
D000567	Amelogenesis Imperfecta	C07.650.800.295.250; C07.793.700.295.250; C16.131.850.800.295.250
D063730	Rickets, Hypophosphatemic	C05.116.198.816.875; C18.452.104.816.875; C18.452.174.845.875; C18.452.750.400.750; C18.654.521.500.133.770.734.875
C536606	Amelogenesis Imperfecta hypomaturation type (supp.)
C567706	Amelogenesis Imperfecta, Hypomaturation Type, Iia3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
Benzo(a)pyrene	affects methylation, decreases expression	3
Panobinostat	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation	2
methyleugenol	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dimethylarsinous acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	decreases expression	1
Zoledronic Acid	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Demecolcine	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

18 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03644706	PHASE3	TERMINATED	Study Evaluating Subjects With Distal Renal Tubular Acidosis
NCT01237288	PHASE3	COMPLETED	Therapeutic Use of Oral Sodium Phosphate (Z-521) in Primary Hypophosphatemic Rickets
NCT03581591	PHASE3	COMPLETED	Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets
NCT00473187	PHASE1	UNKNOWN	Effects of GH on Body Proportions and Final Height in X-Linked Hypophosphatemic Rickets
NCT03748966	EARLY_PHASE1	COMPLETED	Calcitriol Monotherapy for X-Linked Hypophosphatemia
NCT00844740	Not specified	WITHDRAWN	Calcimimetics in Hypophosphatemic Rickets
NCT01578824	Not specified	COMPLETED	Assessment Of Vitamin D Role In The Pathogenesis Of Asthma In Vitamin D Resistent Patients
NCT03348644	Not specified	COMPLETED	Milk Products in the Treatment of Hypophosphatemic Rickets
NCT03651505	Not specified	ACTIVE_NOT_RECRUITING	X-linked Hypophosphatemia Disease Monitoring Program
NCT04184661	Not specified	COMPLETED	Burosumab and 1-25 (OH) Vitamin D on Human Osteoclasts
NCT01746121	Not specified	TERMINATED	Amelogenesis Imperfecta
NCT02994862	Not specified	UNKNOWN	E. Max Laminate Veneers With and Without Using Galla Chinnesis as Natural Cross Linking and Remineralizing Agent
NCT03810859	Not specified	UNKNOWN	Non-syndromic Inherited Anomalies of Mineralized Tooth Tissues: a Whole Exome Study to Identify New Pathogenic Variants
NCT04704089	Not specified	RECRUITING	Colorimetric, Ultra-structural and Elemental Comparison of Dental Enamel Defects
NCT04897724	Not specified	UNKNOWN	Clinical Performance of Composites in Patients With Amelogenesis Imperfecta
NCT04927962	Not specified	COMPLETED	Psycho-social Impact of Amelogenesis and Dentinogenesis Imperfecta
NCT05343247	Not specified	COMPLETED	Dental Age Estimation by Different Methods in Patients With Amelogenesis Imperfecta
NCT07250906	Not specified	RECRUITING	Oral Health Related Quality of Life of Children With Amelogenesis Imperfecta