EDARADD

Summary

EDARADD (EDAR associated via death domain, HGNC:14341) is a protein-coding gene on chromosome 1q42.3-q43, encoding Ectodysplasin-A receptor-associated adapter protein (Q8WWZ3). Adapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs.

This gene was identified by its association with ectodermal dysplasia, a genetic disorder characterized by defective development of hair, teeth, and eccrine sweat glands. The protein encoded by this gene is a death domain-containing protein, and is found to interact with EDAR, a death domain receptor known to be required for the development of hair, teeth and other ectodermal derivatives. This protein and EDAR are coexpressed in epithelial cells during the formation of hair follicles and teeth. Through its interaction with EDAR, this protein acts as an adaptor, and links the receptor to downstream signaling pathways. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Source: NCBI Gene 128178 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant (Strong, GenCC) — +5 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 194 total — 8 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 72
• MANE Select transcript: NM_145861

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14341
Approved symbol	EDARADD
Name	EDAR associated via death domain
Location	1q42.3-q43
Locus type	gene with protein product
Status	Approved
Aliases	CR
Ensembl gene	ENSG00000186197
Ensembl biotype	protein_coding
OMIM	606603
Entrez	128178

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000334232, ENST00000359362, ENST00000439430, ENST00000637660, ENST00000642595

RefSeq mRNA: 3 — MANE Select: NM_145861 NM_001422628, NM_080738, NM_145861

CCDS: CCDS1610, CCDS31065

Canonical transcript exons

ENST00000334232 — 6 exons

Exon	Start	End
ENSE00001424242	236394286	236394505
ENSE00001715490	236468231	236468276
ENSE00001765982	236427392	236427450
ENSE00001797060	236414260	236414299
ENSE00003691258	236409216	236409274
ENSE00003902490	236482267	236484930

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 88.52.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7238 / max 1538.9156, expressed in 594 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9222	1.6937	191
9227	0.9559	443
9228	0.4673	186
9219	0.1923	29
9226	0.1155	65
9224	0.0646	30
9229	0.0508	16
9221	0.0506	13
9225	0.0443	14
9223	0.0420	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	88.52	gold quality
sural nerve	UBERON:0015488	84.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.45	gold quality
pancreas	UBERON:0001264	73.60	gold quality
body of stomach	UBERON:0001161	70.48	gold quality
skin of abdomen	UBERON:0001416	70.47	gold quality
esophagus mucosa	UBERON:0002469	69.71	gold quality
stomach	UBERON:0000945	68.89	gold quality
granulocyte	CL:0000094	68.81	gold quality
body of pancreas	UBERON:0001150	67.40	gold quality
skin of leg	UBERON:0001511	67.40	gold quality
right lobe of thyroid gland	UBERON:0001119	67.17	gold quality
left lobe of thyroid gland	UBERON:0001120	67.10	gold quality
cortical plate	UBERON:0005343	66.38	gold quality
thyroid gland	UBERON:0002046	66.22	gold quality
zone of skin	UBERON:0000014	65.62	gold quality
left testis	UBERON:0004533	65.36	gold quality
urinary bladder	UBERON:0001255	64.95	gold quality
right testis	UBERON:0004534	64.20	gold quality
testis	UBERON:0000473	63.88	gold quality
lower esophagus mucosa	UBERON:0035834	63.49	gold quality
fundus of stomach	UBERON:0001160	61.51	gold quality
minor salivary gland	UBERON:0001830	61.45	gold quality
prostate gland	UBERON:0002367	60.98	gold quality
lymph node	UBERON:0000029	60.60	gold quality
apex of heart	UBERON:0002098	60.40	gold quality
leukocyte	CL:0000738	59.91	gold quality
metanephros cortex	UBERON:0010533	59.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	17.24
E-ANND-3	yes	8.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting EDARADD, 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-1252-5P	100.00	69.80	2774
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-8067	99.86	69.59	2260
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-7854-3P	99.08	66.26	1117

Literature-anchored findings (GeneRIF, showing 16)

• interacts with the death domain of Edar and links the receptor to downstream signalling pathways (PMID:11780064)
• crinkled binds EDAR through a homotypic death domain interaction and mediates engagement of the NF-kappaB pathway, possibly by recruiting TRAF2 to the receptor-signaling complex (PMID:11882293)
• Results demonstrate that EDARADD mutations are not a frequent cause of hypohidrotic ectodermal dysplasia, while mutations in TRAF6, TAB2 and TAK1 may not be implicated in this disease. (PMID:20222921)
• The phenotypes associated with EDA1, EDAR, and EDARADD mutations were indistinguishable (PMID:20979233)
• a cohort of 93 Swedish probands with non-syndromic, isolated oligodontia, mutations were identified in the EDARADD), AXIN2, MSX1, and PAX9 genes (PMID:21626677)
• The study data demonstrate an association between SNP rs3916983 of the EDARADD gene and non-syndromic hypodontia in Chinese Han individuals. (PMID:22984994)
• detected a novel missense mutation c.367G>A (p.Asp123Asn) in the death domain of the gene EDARADD, which co-segregated with hypohidrotic ectodermal dysplasia in the affected family. This mutation led to an impaired ability of EDARADD to activate NF-kappaB signaling. (PMID:26440664)
• report a mutation consisting of the first gross deletion identified in this gene (c.131-?_189+?del), with a recessive mode of inheritance (PMID:30022538)
• study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in Hypohidrotic ectodermal dysplasia and 44.4% in non-syndromic tooth agenesis. (PMID:31796081)
• Alterations in the methylome of the stromal tumour microenvironment signal the presence and severity of prostate cancer. (PMID:32188493)
• Homozygous variants of EDAR underlying hypohidrotic ectodermal dysplasia in three consanguineous families. (PMID:32819890)
• Characterization of EDARADD gene mutations responsible for hypohidrotic ectodermal dysplasia. (PMID:34219261)
• Gene Mutations of the Three Ectodysplasin Pathway Key Players (EDA, EDAR, and EDARADD) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations. (PMID:34573371)
• EDARADD silencing suppresses the proliferation and migration of bladder cancer cells. (PMID:35637063)
• A new variant of the ectodysplasin A receptor death domain gene associated with anhidrotic ectodermal dysplasia in a Turkish family and its simple diagnosis by restriction fragment length polymorphism. (PMID:37673591)
• EDARADD promotes colon cancer progression by suppressing E3 ligase Trim21-mediated ubiquitination and degradation of Snail. (PMID:37838280)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Edaradd	ENSMUSG00000095105
rattus_norvegicus	Edaradd	ENSRNOG00000002624

Protein

Protein identifiers

Ectodysplasin-A receptor-associated adapter protein — Q8WWZ3 (reviewed: Q8WWZ3)

Alternative names: EDAR-associated death domain protein, Protein crinkled homolog

All UniProt accessions (4): A0A1B0GV26, A0A2R8Y5E0, B1AL55, Q8WWZ3

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs. Mediates the activation of NF-kappa-B.

Subunit / interactions. Self-associates and binds EDAR, TRAF1, TRAF2 and TRAF3.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in adult pancreas, placenta and fetal skin, and at lower levels in lung, thymus, prostate and testis.

Disease relevance. Ectodermal dysplasia 11A, hypohidrotic/hair/nail type, autosomal dominant (ECTD11A) [MIM:614940] A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands. The disease is caused by variants affecting the gene represented in this entry. Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (ECTD11B) [MIM:614941] A disorder due to abnormal development of two or more ectodermal structures, and characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WWZ3-1	A	yes
Q8WWZ3-2	B

RefSeq proteins (3): NP_001409557, NP_542776, NP_665860* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR039200	EDARADD	Family

Pfam: PF00531

UniProt features (12 total): sequence variant 6, region of interest 2, chain 1, domain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWZ3-F1	73.81	0.44

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5669034	TNFs bind their physiological receptors

MSigDB gene sets: 230 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, MARTINEZ_RB1_TARGETS_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, ZHANG_BREAST_CANCER_PROGENITORS_UP, AML1_01, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, TTTGCAC_MIR19A_MIR19B, BOYLAN_MULTIPLE_MYELOMA_C_D_UP, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, VANASSE_BCL2_TARGETS_DN, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, LIM_MAMMARY_STEM_CELL_UP

GO Biological Process (2): signal transduction (GO:0007165), cell differentiation (GO:0030154)

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

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TNFR2 non-canonical NF-kB pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular developmental process	1
binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDARADD	EDAR	Q9UNE0	989
EDARADD	EDA	Q92838	922
EDARADD	WNT10A	Q9GZT5	728
EDARADD	EDA2R	Q9HAV5	728
EDARADD	PAX9	P55771	671
EDARADD	PDE4C	Q08493	599
EDARADD	WNT10B	O00744	591
EDARADD	TRAF6	Q9Y4K3	587
EDARADD	MSX1	P28360	583
EDARADD	ELOVL2	Q9NXB9	581
EDARADD	TOM1L1	O75674	572
EDARADD	TAB2	Q9NYJ8	551
EDARADD	ELOVL5	Q9NYP7	517
EDARADD	ERO1B	Q86YB8	510
EDARADD	AXIN2	Q9Y2T1	507

IntAct

41 interactions, top by confidence:

A	B	Type	Score
NTAQ1	EDARADD	psi-mi:“MI:0915”(physical association)	0.670
EDARADD	NTAQ1	psi-mi:“MI:0915”(physical association)	0.670
EDARADD	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	SDCBP	psi-mi:“MI:0915”(physical association)	0.560
SUMO1	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
SHPRH	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
SUMO1P1	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
RNF111	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
TRAF6	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	SUMO1	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	SHPRH	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	RNF111	psi-mi:“MI:0915”(physical association)	0.560
EDARADD	TRAF6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (24): EDARADD (Two-hybrid), EDARADD (Two-hybrid), EDARADD (Two-hybrid), EDARADD (Two-hybrid), EDARADD (Two-hybrid), EDARADD (Two-hybrid), EDARADD (Two-hybrid), EDARADD (Two-hybrid), SHPRH (Two-hybrid), SUMO1P1 (Two-hybrid), EDARADD (Protein-RNA), EDARADD (Reconstituted Complex), TRAF2 (Affinity Capture-Western), EDARADD (Affinity Capture-Western), EDARADD (Affinity Capture-MS)

ESM2 similar proteins: A0JNM1, A2A9G7, A6NFA0, A7MB05, D3ZJ47, F1M5M3, F1MJR8, K9JA28, O35664, O88472, P16872, P48551, Q02223, Q0VFL4, Q13651, Q14B48, Q1RMT9, Q29RT9, Q4W815, Q56A20, Q5DU28, Q5DW34, Q5R7R7, Q5RBQ2, Q5RCS3, Q5SW75, Q60664, Q61727, Q63HN8, Q6NRK3, Q6UWV7, Q6ZRS4, Q76I76, Q7M6U3, Q7TMJ8, Q80WK2, Q810S2, Q86UW2, Q8K2J4, Q8K3V7

Diamond homologs: Q8VHX2, Q8WWZ3, Q95LN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	9
Uncertain significance	103
Likely benign	14
Benign	41

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
2428490	NM_145861.4(EDARADD):c.469G>A (p.Glu157Lys)	Pathogenic
253093	NM_145861.4(EDARADD):c.120+1G>A	Pathogenic
280481	NM_145861.4(EDARADD):c.196C>T (p.Arg66Ter)	Pathogenic
2939815	NC_000001.11:g.236468231_236468234del	Pathogenic
4189	NM_145861.4(EDARADD):c.365T>G (p.Leu122Arg)	Pathogenic
473077	NM_145861.4(EDARADD):c.417G>A (p.Trp139Ter)	Pathogenic
996824	NM_145861.4(EDARADD):c.85G>A (p.Glu29Lys)	Pathogenic
996825	NM_145861.4(EDARADD):c.570C>A (p.Asp190Glu)	Pathogenic
1333297	NM_145861.4(EDARADD):c.359A>C (p.Asp120Ala)	Likely pathogenic
1347024	NC_000001.10:g.(?236631511)(236631596_?)dup	Likely pathogenic
253092	NM_145861.4(EDARADD):c.367G>A (p.Asp123Asn)	Likely pathogenic
3581597	NM_145861.4(EDARADD):c.61+1G>C	Likely pathogenic
4188	NM_145861.4(EDARADD):c.454G>A (p.Glu152Lys)	Likely pathogenic
4277299	NM_145861.4(EDARADD):c.359A>T (p.Asp120Val)	Likely pathogenic
452073	NM_145861.4(EDARADD):c.389A>G (p.Asp130Gly)	Likely pathogenic
4685519	NM_145861.4(EDARADD):c.548G>T (p.Cys183Phe)	Likely pathogenic
929423	NM_145861.4(EDARADD):c.413A>T (p.Asn138Ile)	Likely pathogenic

SpliceAI

1080 predictions. Top by Δscore:

Variant	Effect	Δscore
1:236414248:T:A	acceptor_gain	1.0000
1:236414258:A:AG	acceptor_gain	1.0000
1:236414259:G:GG	acceptor_gain	1.0000
1:236427388:CTAGC:C	acceptor_loss	1.0000
1:236427389:TAG:T	acceptor_loss	1.0000
1:236427390:A:AG	acceptor_gain	1.0000
1:236427391:G:GT	acceptor_gain	1.0000
1:236427450:GGTA:G	donor_loss	1.0000
1:236427452:T:G	donor_loss	1.0000
1:236482265:A:AG	acceptor_gain	1.0000
1:236482266:G:GG	acceptor_gain	1.0000
1:236394502:GAGG:G	donor_gain	0.9900
1:236394504:GG:G	donor_gain	0.9900
1:236394505:GG:G	donor_gain	0.9900
1:236409210:TTACA:T	acceptor_loss	0.9900
1:236409211:TACA:T	acceptor_loss	0.9900
1:236409212:ACAG:A	acceptor_loss	0.9900
1:236409213:CA:C	acceptor_loss	0.9900
1:236409214:A:AG	acceptor_gain	0.9900
1:236409214:A:C	acceptor_loss	0.9900
1:236409215:G:GA	acceptor_gain	0.9900
1:236409215:GATC:G	acceptor_gain	0.9900
1:236409273:TGGT:T	donor_loss	0.9900
1:236409275:G:A	donor_loss	0.9900
1:236409276:TA:T	donor_loss	0.9900
1:236414257:C:G	acceptor_gain	0.9900
1:236414259:GTC:G	acceptor_gain	0.9900
1:236414259:GTCA:G	acceptor_gain	0.9900
1:236425360:G:T	donor_gain	0.9900
1:236427391:GC:G	acceptor_gain	0.9900

AlphaMissense

1447 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:236482416:T:A	W139R	0.999
1:236482416:T:C	W139R	0.999
1:236482418:G:C	W139C	0.999
1:236482418:G:T	W139C	0.999
1:236482387:T:C	L129P	0.998
1:236482437:T:A	W146R	0.998
1:236482437:T:C	W146R	0.998
1:236482565:G:C	R188S	0.998
1:236482565:G:T	R188S	0.998
1:236482429:C:A	A143E	0.997
1:236482504:T:C	L168S	0.997
1:236482537:T:C	L179P	0.997
1:236482564:G:C	R188T	0.997
1:236482564:G:T	R188M	0.997
1:236482336:T:A	I112K	0.996
1:236482411:A:T	K137I	0.996
1:236482415:C:A	N138K	0.996
1:236482415:C:G	N138K	0.996
1:236482421:G:C	R140S	0.996
1:236482421:G:T	R140S	0.996
1:236482501:T:C	F167S	0.996
1:236482426:T:C	F142S	0.995
1:236482387:T:A	L129Q	0.994
1:236482417:G:C	W139S	0.994
1:236482459:T:C	L153S	0.994
1:236482485:A:C	S162R	0.994
1:236482487:C:A	S162R	0.994
1:236482487:C:G	S162R	0.994
1:236482548:T:C	C183R	0.994
1:236482563:A:G	R188G	0.994

dbSNP variants (sampled 300 via entrez): RS1000021446 (1:236413574 T>C), RS1000061859 (1:236423926 T>C), RS1000079036 (1:236442737 C>T), RS1000083461 (1:236455317 T>G), RS1000091046 (1:236398301 T>G), RS1000161525 (1:236468481 G>C), RS1000213041 (1:236404063 G>A), RS1000230159 (1:236448899 A>G), RS1000244234 (1:236403769 G>A,T), RS1000251891 (1:236466247 C>T), RS1000282610 (1:236467594 G>A), RS1000309525 (1:236419500 A>G), RS1000376537 (1:236432843 C>A), RS1000501337 (1:236416218 C>T), RS1000542946 (1:236479352 A>G)

Disease associations

OMIM: gene MIM:606603 | disease phenotypes: MIM:614941, MIM:614940, MIM:305100, MIM:224900, MIM:129490

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant	Strong	Autosomal dominant
ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive	Strong	Autosomal recessive
hypohidrotic ectodermal dysplasia	Strong	Semidominant
autosomal dominant hypohidrotic ectodermal dysplasia	Supportive	Autosomal dominant
autosomal recessive hypohidrotic ectodermal dysplasia	Supportive	Autosomal recessive
tooth agenesis	Supportive	Autosomal dominant

Mondo (9): hypohidrotic ectodermal dysplasia (MONDO:0016535), ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (MONDO:0013983), ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant (MONDO:0013982), ectodermal dysplasia syndrome (MONDO:0019287), ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (MONDO:0009147), ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (MONDO:0007509), autosomal dominant hypohidrotic ectodermal dysplasia (MONDO:0015884), autosomal recessive hypohidrotic ectodermal dysplasia (MONDO:0016619), tooth agenesis (MONDO:0005486)

Orphanet (4): Hypohidrotic ectodermal dysplasia (Orphanet:238468), Autosomal recessive hypohidrotic ectodermal dysplasia (Orphanet:248), Autosomal dominant hypohidrotic ectodermal dysplasia (Orphanet:1810), Ectodermal dysplasia syndrome (Orphanet:79373)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000202	Orofacial cleft
HP:0000217	Xerostomia
HP:0000232	Everted lower lip vermilion
HP:0000457	Depressed nasal ridge
HP:0000561	Absent eyelashes
HP:0000607	Periorbital wrinkles
HP:0000653	Sparse eyelashes
HP:0000668	Hypodontia
HP:0000674	Anodontia
HP:0000677	Oligodontia
HP:0000679	Taurodontia
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000687	Widely spaced teeth
HP:0000689	Dental malocclusion
HP:0000690	Agenesis of maxillary lateral incisor
HP:0000691	Microdontia
HP:0000696	Delayed eruption of permanent teeth
HP:0000698	Conical tooth
HP:0000958	Dry skin
HP:0000963	Thin skin
HP:0000964	Eczematoid dermatitis
HP:0000966	Hypohidrosis
HP:0000968	Ectodermal dysplasia
HP:0000970	Anhidrosis
HP:0001000	Abnormality of skin pigmentation
HP:0001106	Periorbital hyperpigmentation

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002826_3	Urate levels (BMI interaction)	6.000000e-06
GCST002827_2	Urate levels (BMI interaction)	1.000000e-07
GCST010571_9	Autoimmune thyroid disease	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004476	Ectodermal Dysplasia	C16.131.077.350; C16.131.831.350; C16.320.850.250; C17.800.804.350; C17.800.827.250
D053360	Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive	C16.131.077.350.348; C16.131.831.350.348; C16.320.850.250.348; C17.800.804.350.348; C17.800.827.250.348

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases methylation	3
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, decreases expression	1
2-anisidine	affects expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	decreases reaction, increases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
corosolic acid	decreases expression	1
azaspiracid	increases expression	1
lipopolysaccharide, E. coli O26-B6	increases expression, decreases reaction	1
ICG 001	increases expression	1
abrine	decreases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	decreases reaction, increases expression	1
(+)-JQ1 compound	decreases 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
Bortezomib	increases expression	1
Resveratrol	decreases reaction, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Curcumin	decreases reaction, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Oxygen	decreases reaction, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01470235	Not specified	UNKNOWN	Hypodontia and Ovarian Cancer
NCT03445026	Not specified	UNKNOWN	Frequency of Hypodontia After Chemotherapy in Childhood Cancer Survivors Study
NCT05771246	Not specified	COMPLETED	Craniofacial Morphology And Sella Turcica Bridging Associated With Third Molar Agenesis.
NCT01109290	Not specified	COMPLETED	Characterization of Sweat Gland Function in Patients With Recessively Inherited Hypohidrotic Ectodermal Dysplasia
NCT01293565	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected by Hypohidrotic Ectodermal Dysplasia - A
NCT01386775	Not specified	COMPLETED	Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia: Intrafamilial Variation
NCT01398397	Not specified	COMPLETED	Medical Record Review of Hypohidrotic Ectodermal Dysplasia Clinical Phenotype
NCT01398813	Not specified	COMPLETED	X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Carrier Outlook Toward Reproduction Survey
NCT01629927	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia (ECP-012)
NCT01629940	Not specified	COMPLETED	Phenotypic and Genetic Properties in Males at Risk for X-linked Hypohidrotic Ectodermal Dysplasia: Evaluation of an Early Diagnosis Technology and Tests to Assess Nutritional Status
NCT04741412	Not specified	COMPLETED	Pediatric SARS-CoV-2 Infections: Course of COVID-19, Immune Responses, Complications and Long-term Consequences
NCT05378932	Not specified	COMPLETED	Impact of Dysregulation of Core Body Temperature on Sleep in Patients With Hypohidrotic Ectodermal Dysplasia
NCT00001211	Not specified	COMPLETED	Clinical Study of Oral Endosseous Titanium Implants in Edentulous Subjects
NCT00266513	Not specified	TERMINATED	Studies of Disorders in Antibody Production and Related Primary Immunodeficiency States
NCT01108770	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia
NCT02896387	Not specified	TERMINATED	Ability of a Molecule (Prima) to Restore Physiological Differentiation in Epithelium Expressing Gene p63
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07468019	Not specified	RECRUITING	Organization’s Unique Protocol ID