EDA2R

Summary

EDA2R (ectodysplasin A2 receptor, HGNC:17756) is a protein-coding gene on chromosome Xq12, encoding Tumor necrosis factor receptor superfamily member 27 (Q9HAV5). Receptor for EDA isoform A2, but not for EDA isoform A1.

The protein encoded by this gene is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily, and contains cysteine-rich repeats and a single transmembrane domain. This protein binds to the EDA-A2 isoform of ectodysplasin, which plays an important role in maintenance of hair and teeth. Alternatively spliced transcript variants encodes distinct protein isoforms.

Source: NCBI Gene 60401 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked hypohidrotic ectodermal dysplasia (Supportive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 98 total — 1 likely-pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_021783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17756
Approved symbol	EDA2R
Name	ectodysplasin A2 receptor
Location	Xq12
Locus type	gene with protein product
Status	Approved
Aliases	XEDAR, EDA-A2R, EDAA2R, TNFRSF27
Ensembl gene	ENSG00000131080
Ensembl biotype	protein_coding
OMIM	300276
Entrez	60401

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000253392, ENST00000374719, ENST00000396050, ENST00000451436, ENST00000902728, ENST00000902729, ENST00000902730, ENST00000902731, ENST00000902732, ENST00000925064, ENST00000944243, ENST00000944244

RefSeq mRNA: 9 — MANE Select: NM_021783 NM_001199687, NM_001242310, NM_001324199, NM_001324201, NM_001324202, NM_001324204, NM_001324205, NM_001324206, NM_021783

CCDS: CCDS14386, CCDS56603

Canonical transcript exons

ENST00000374719 — 7 exons

Exon	Start	End
ENSE00000897926	66602633	66602797
ENSE00000897935	66605048	66605226
ENSE00001302968	66604421	66604506
ENSE00001428830	66638995	66639078
ENSE00001663009	66599474	66599860
ENSE00001863772	66595637	66598093
ENSE00003720717	66615934	66616030

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 85.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0474 / max 108.5483, expressed in 1148 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199509	2.5699	912
199508	2.1957	785
199510	1.2818	711

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	85.65	gold quality
type B pancreatic cell	CL:0000169	85.39	gold quality
stromal cell of endometrium	CL:0002255	83.67	gold quality
right adrenal gland cortex	UBERON:0035827	80.28	gold quality
hair follicle	UBERON:0002073	80.14	gold quality
right uterine tube	UBERON:0001302	80.04	gold quality
descending thoracic aorta	UBERON:0002345	79.42	gold quality
diaphragm	UBERON:0001103	79.37	gold quality
ascending aorta	UBERON:0001496	78.85	gold quality
thoracic aorta	UBERON:0001515	78.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.46	gold quality
right adrenal gland	UBERON:0001233	78.43	gold quality
smooth muscle tissue	UBERON:0001135	77.58	gold quality
left adrenal gland	UBERON:0001234	76.98	gold quality
mucosa of urinary bladder	UBERON:0001259	76.61	gold quality
endocervix	UBERON:0000458	76.12	gold quality
left adrenal gland cortex	UBERON:0035825	76.03	gold quality
adrenal cortex	UBERON:0001235	76.00	gold quality
left ovary	UBERON:0002119	75.05	gold quality
body of uterus	UBERON:0009853	74.98	gold quality
aorta	UBERON:0000947	74.61	gold quality
apex of heart	UBERON:0002098	74.47	gold quality
adrenal gland	UBERON:0002369	74.39	gold quality
calcaneal tendon	UBERON:0003701	74.27	gold quality
right ovary	UBERON:0002118	73.43	gold quality
thymus	UBERON:0002370	73.34	silver quality
left lobe of thyroid gland	UBERON:0001120	73.20	gold quality
ectocervix	UBERON:0012249	73.03	gold quality
right coronary artery	UBERON:0001625	72.62	gold quality
left coronary artery	UBERON:0001626	72.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	180.68
E-ANND-3	no	2.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

99 targeting EDA2R, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 22)

• Results establish a major role of TRAF3 and -6 in X-linked ectodermal dysplasia receptor (XEDAR) signaling and in the process of ectodermal differentiation. (PMID:12270937)
• XEDAR belongs to a novel class of death receptors that lack a discernible death domain but are capable of activating apoptosis in a caspase 8- and FADD-dependent fashion (PMID:15280356)
• isoforms of EDA-A5 and A5’,activated NF-kappaB through receptors EDAR and XEDAR (PMID:16423472)
• The androgen receptor gene and EDA2R are significantly associated with androgenetic alopecia. (PMID:18385763)
• androgen receptor/ectodysplasin A2 receptor haplotype may have a role in male pattern baldness (PMID:19373488)
• XEDAR is a putative tumor suppressor that could prevent malignant transformation and tumor progression by regulating apoptosis and anoikis. (PMID:19543321)
• because no frequent variant other than rs1385699 has been reported in EDA2R in the European population, it is probable that the causative variant(s) modifies the expression of one or more flanking genes, i.e. AR and EDA2R (PMID:20199557)
• A crucial role of the EDA-A2/ectodysplasin A2 (XEDAR) interaction is revealed in the p53-signaling pathway. (PMID:20501644)
• association in dental crowding in the Hong Kong Chinese population (PMID:21724072)
• The results suggest that EDA2R confers susceptibility to early onset female pattern hair loss (PMID:22309448)
• To investigate the evolutionary history of the EDA2R/AR intergenic region, we characterized the haplotype structure of 52 of its highly differentiated SNPs. Nearly all human X chromosomes carry one of two modal haplotypes for these 52 SNPs. (PMID:23959643)
• XEDAR activates the non-canonical NF-kappaB pathway. (PMID:26260321)
• EDA-A2 and its receptor XEDAR are overexpressed in epithelial cells of salivary glands in Sjogren’s syndrome patients, in comparison with healthy individuals. The EDA-A2/XEDAR system in these cells is involved in the induction of apoptosis via CASP3 activation. (PMID:26659383)
• We found evidence for AR but not EDA2R as the candidate gene at the androgenetic alopecia risk locus on chromosome X. (PMID:27060448)
• The upregulation of SPOCK2-encoded Testican2 proteoglycan and of ectodysplasin (EDA) protein was coupled with a down-regulation of EDA2 receptor (EDA2R). (PMID:29708036)
• Expression of EDA2R in human hair follicles.EDA-A2/EDA2R signaling could inhibit hair growth. (PMID:31607478)
• EDA2R mediates podocyte injury in high glucose milieu. (PMID:32304771)
• Ectodysplasin-A2 induces dickkopf 1 expression in human balding dermal papilla cells overexpressing the ectodysplasin A2 receptor. (PMID:32736705)
• EDA2R-NIK signalling promotes muscle atrophy linked to cancer cachexia. (PMID:37165186)
• Ectodysplasin A2 receptor-NF-kappaB-inducing kinase axis: a new player in muscle wasting to cancer cachexia. (PMID:37807033)
• Expression of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Candidate Genes EDA2R, PCDH9, and TRAF7 in Normal Human Kidney Development and CAKUT. (PMID:38927638)
• This study indicates that ectodysplasin A2 receptor may be a biomarker for aging, especially in the context of skeletal muscle, and targeting it could be a potential strategy to mitigate aging-related phenotypes. (PMID:39988718)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eda2r	ENSMUSG00000034457
rattus_norvegicus	Eda2r	ENSRNOG00000013018

Paralogs (2): TNFRSF19 (ENSG00000127863), EDAR (ENSG00000135960)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 27 — Q9HAV5 (reviewed: Q9HAV5)

Alternative names: X-linked ectodysplasin-A2 receptor

All UniProt accessions (1): Q9HAV5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for EDA isoform A2, but not for EDA isoform A1. Mediates the activation of the NF-kappa-B and JNK pathways. Activation seems to be mediated by binding to TRAF3 and TRAF6.

Subunit / interactions. Associates with TRAF1, TRAF3 and TRAF6.

Subcellular location. Membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HAV5-1	1	yes
Q9HAV5-2	2, Long
Q9HAV5-3	3

RefSeq proteins (9): NP_001186616, NP_001229239, NP_001311128, NP_001311130, NP_001311131, NP_001311133, NP_001311134, NP_001311135, NP_068555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR022319	TNFR_27	Family
IPR034060	TNFRSF27_N	Domain
IPR047526	TNR19/27/EDAR	Family

Pfam: PF00020

UniProt features (24 total): disulfide bond 8, repeat 3, topological domain 2, splice variant 2, sequence variant 2, chain 1, transmembrane region 1, mutagenesis site 1, sequence conflict 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAV5-F1	69.14	0.37

Functional residue map

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

Disulfide bonds (8): 3–15, 18–31, 21–41, 44–58, 61–75, 64–83, 86–104, 107–118

Glycosylation sites (1): 74

Mutagenesis-validated functional residues (1):

Position	Phenotype
256	abolishes traf6 association.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 142 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_ECTODERM_DEVELOPMENT, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_JNK_CASCADE, GOBP_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, GOBP_POSITIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (8): epidermis development (GO:0008544), ectodermal cell differentiation (GO:0010668), cytokine-mediated signaling pathway (GO:0019221), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of JNK cascade (GO:0046330), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), cell differentiation (GO:0030154), tumor necrosis factor-mediated signaling pathway (GO:0033209)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), tumor necrosis factor receptor activity (GO:0005031), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

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
tissue development	1
ectoderm development	1
cell differentiation	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
cellular developmental process	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
signaling receptor activity	1
death receptor activity	1
tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor binding	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDA2R	EDA	Q92838	967
EDA2R	SLC24A5	Q71RS6	828
EDA2R	SLC45A2	Q9UMX9	788
EDA2R	TRAF6	Q9Y4K3	739
EDA2R	EDARADD	Q8WWZ3	728
EDA2R	TRAF3	Q13114	690
EDA2R	CYLD	Q9NQC7	671
EDA2R	TNF	P01375	652
EDA2R	TNFRSF1A	P19438	623
EDA2R	CD40	P25942	573
EDA2R	TNFRSF17	Q02223	501
EDA2R	AR	P10275	474
EDA2R	IKBKG	Q9Y6K9	456
EDA2R	HEPH	Q9BQS7	454
EDA2R	FASLG	P48023	444

IntAct

38 interactions, top by confidence:

A	B	Type	Score
TRAF6	EDA2R	psi-mi:“MI:0915”(physical association)	0.670
TRAF3	EDA2R	psi-mi:“MI:0915”(physical association)	0.670
STRIT1	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
SGTA	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
AGR3	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
PLP1	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
NKG7	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
TMEM262	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
EDA2R	ICAM1	psi-mi:“MI:0914”(association)	0.530
Eda2r	EDA2R	psi-mi:“MI:0915”(physical association)	0.400
CASP8	EDA2R	psi-mi:“MI:0915”(physical association)	0.400
CASP10	EDA2R	psi-mi:“MI:0915”(physical association)	0.400
FADD	EDA2R	psi-mi:“MI:0915”(physical association)	0.400
C1QB	EDA2R	psi-mi:“MI:0915”(physical association)	0.370
CEBPE	EDA2R	psi-mi:“MI:0915”(physical association)	0.370
EDA2R	TK1	psi-mi:“MI:0914”(association)	0.350
STRIT1	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
PLP1	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
ATP6V0C	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
NKG7	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
GIMAP5	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
SGTA	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
JAGN1	EDA2R	psi-mi:“MI:0915”(physical association)	0.000
AGR3	EDA2R	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): HSDL1 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), TRAF2 (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), TK1 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), TRAF6 (Affinity Capture-MS), TRAF1 (Affinity Capture-MS), EDA2R (Synthetic Lethality), TRAF3 (Affinity Capture-MS), TRAF6 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), TRAF1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), TK1 (Affinity Capture-MS)

ESM2 similar proteins: D3ZF92, D5K8A9, O00220, O14763, O15553, O35305, O35714, O75509, P12342, P20333, P22934, P25118, P25119, P26898, P27987, P28908, P50284, P97525, Q2YDG7, Q3U4N7, Q5HZW5, Q5ND28, Q5PQX1, Q60846, Q80WY6, Q86T13, Q86VZ4, Q8BX35, Q8BZW2, Q8CB67, Q8IY92, Q8NC42, Q8TBE3, Q8VCP9, Q8WWF5, Q90VY2, Q921T2, Q96L08, Q9DA48, Q9EPU5

Diamond homologs: Q8BX35, Q9HAV5, Q9JLL3, Q9N092, Q9NS68, O95407, Q08DP3, Q2KI80, Q5FVJ4, Q8BRJ3, Q8BX43, Q8IUW5, Q8K2J7, Q8NC24, Q969Z4, Q5F3A4, O35305, Q90VY2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EDA	up-regulates	EDA2R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	47
Likely benign	17
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3381213	NM_021783.5(EDA2R):c.620del (p.Asn207fs)	Likely pathogenic

SpliceAI

1489 predictions. Top by Δscore:

Variant	Effect	Δscore
X:66602632:CCA:C	donor_gain	1.0000
X:66602632:CCACG:C	donor_gain	1.0000
X:66602793:GGCAC:G	acceptor_gain	1.0000
X:66602795:CAC:C	acceptor_gain	1.0000
X:66602796:AC:A	acceptor_gain	1.0000
X:66602797:CC:C	acceptor_gain	1.0000
X:66602797:CCT:C	acceptor_loss	1.0000
X:66602798:C:CC	acceptor_gain	1.0000
X:66602798:C:CG	acceptor_loss	1.0000
X:66602799:T:A	acceptor_loss	1.0000
X:66615929:CTTA:C	donor_loss	1.0000
X:66615930:TTA:T	donor_loss	1.0000
X:66615931:TA:T	donor_loss	1.0000
X:66615932:A:AC	donor_gain	1.0000
X:66615933:C:CC	donor_gain	1.0000
X:66615933:C:CT	donor_loss	1.0000
X:66616026:GAAGG:G	acceptor_gain	1.0000
X:66616028:AGG:A	acceptor_gain	1.0000
X:66616029:GG:G	acceptor_gain	1.0000
X:66616031:C:CC	acceptor_gain	1.0000
X:66602627:CCTT:C	donor_loss	0.9900
X:66602628:CTTAC:C	donor_loss	0.9900
X:66602629:TTA:T	donor_loss	0.9900
X:66602630:TACCA:T	donor_loss	0.9900
X:66602631:A:AA	donor_loss	0.9900
X:66602631:A:AC	donor_gain	0.9900
X:66602632:C:CC	donor_gain	0.9900
X:66602632:C:CG	donor_loss	0.9900
X:66602632:C:CT	donor_gain	0.9900
X:66602794:GCAC:G	acceptor_gain	0.9900

AlphaMissense

1955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:66604503:G:C	F90L	0.997
X:66604503:G:T	F90L	0.997
X:66604505:A:G	F90L	0.997
X:66604462:C:G	C104S	0.996
X:66604463:A:G	C104R	0.996
X:66604463:A:T	C104S	0.996
X:66605066:C:G	C83S	0.995
X:66605067:A:T	C83S	0.995
X:66605108:C:G	R69P	0.995
X:66605124:A:G	C64R	0.995
X:66605067:A:G	C83R	0.994
X:66605089:G:C	C75W	0.994
X:66605222:C:G	C31S	0.994
X:66605223:A:T	C31S	0.994
X:66604494:C:A	K93N	0.993
X:66604494:C:G	K93N	0.993
X:66605091:A:G	C75R	0.993
X:66605222:C:T	C31Y	0.993
X:66605123:C:T	C64Y	0.992
X:66605066:C:T	C83Y	0.991
X:66605090:C:G	C75S	0.991
X:66605090:C:T	C75Y	0.991
X:66605091:A:T	C75S	0.991
X:66605122:A:C	C64W	0.991
X:66605123:C:G	C64S	0.991
X:66605124:A:T	C64S	0.991
X:66605142:A:G	C58R	0.991
X:66615959:C:G	C21S	0.991
X:66615960:A:T	C21S	0.991
X:66604461:G:C	C104W	0.990

dbSNP variants (sampled 300 via entrez): RS1000027902 (X:66602370 C>T), RS1000193095 (X:66615701 C>A), RS1000211244 (X:66611303 A>G), RS1000352625 (X:66625000 G>A,C), RS1000441390 (X:66602879 C>T), RS1000530527 (X:66608833 C>T), RS1000556857 (X:66618011 C>T), RS1000662232 (X:66625397 A>T), RS1000820854 (X:66617879 C>A,T), RS1000885026 (X:66619660 T>A), RS1000890883 (X:66625180 G>A), RS1000946001 (X:66625589 C>T), RS1001164483 (X:66613531 A>G), RS1001195173 (X:66601891 G>A), RS1001322592 (X:66610232 C>A)

Disease associations

OMIM: gene MIM:300276 | disease phenotypes: MIM:106600, MIM:305100

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked hypohidrotic ectodermal dysplasia	Supportive	X-linked

Mondo (2): tooth agenesis (MONDO:0005486), X-linked hypohidrotic ectodermal dysplasia (MONDO:0010585)

Orphanet (4): Oligodontia (Orphanet:99798), X-linked hypohidrotic ectodermal dysplasia (Orphanet:181), Hypohidrotic ectodermal dysplasia (Orphanet:238468), NON RARE IN EUROPE: Hypodontia (Orphanet:2227)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000232	Everted lower lip vermilion
HP:0000457	Depressed nasal ridge
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000822	Hypertension
HP:0000830	Anterior hypopituitarism
HP:0000966	Hypohidrosis
HP:0002007	Frontal bossing
HP:0002231	Sparse body hair
HP:0008070	Sparse hair
HP:0009882	Short distal phalanx of finger
HP:0010803	Everted upper lip vermilion
HP:0100651	Type I diabetes mellitus
HP:0100840	Aplasia/Hypoplasia of the eyebrow

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001297_1	Male-pattern baldness	3.000000e-22
GCST003480_2	Balding	2.000000e-08
GCST003983_1	Male-pattern baldness	1.000000e-247
GCST006661_1	Male-pattern baldness	3.000000e-15
GCST006661_217	Male-pattern baldness	5.000000e-178

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007825	balding measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Tumour necrosis factor (TNF) receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Aflatoxin B1	decreases methylation, increases expression	3
Cadmium Chloride	decreases expression, increases abundance	3
sodium arsenite	increases expression	2
Cadmium	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
securinine	increases expression	1
zinc chromate	increases abundance, increases expression	1
polyhexamethyleneguanidine	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects expression	1
Cisplatin	increases expression	1
Cyclophosphamide	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	affects expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01775462	PHASE2	COMPLETED	Phase 2 Study to Evaluate Safety, Pharmacokinetics, Immunogenicity and Pharmacodynamics/Efficacy of EDI200 in Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
NCT04980638	PHASE2	RECRUITING	Intraamniotic Administrations of ER004 to Male Subjects With X-linked Hypohidrotic Ectodermal Dysplasia
NCT01564225	PHASE1	COMPLETED	A Phase 1, Open-label, Multicenter, Safety and Pharmacokinetic Study of EDI200
NCT01135888	Not specified	COMPLETED	Short Term Effects and Risks of Physical Exercise in Subjects With Hypohidrotic Ectodermal Dysplasia
NCT01308333	Not specified	COMPLETED	Investigation of Chronic Inflammatory Processes in Male Individuals With Hypohidrotic Ectodermal Dysplasia
NCT01342133	Not specified	COMPLETED	Sweat Duct Imaging in Mother/Newborn Dyads
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
NCT01871714	Not specified	COMPLETED	Phenotypic Properties in Individuals Affected With XLHED
NCT01992289	Not specified	UNKNOWN	Extension Study of XLHED-Affected Male Subjects Treated With EDI200 in Protocol ECP-002
NCT02099552	Not specified	COMPLETED	Natural History and Outcomes in X-Linked Hypohidrotic Ectodermal Dysplasia
NCT07096206	Not specified	ACTIVE_NOT_RECRUITING	Characteristics and Impacts of X-linked Hypohidrotic Ectodermal Dysplasia (XLHED) in Boys: An Observational International Study
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.