TSPEAR

Summary

TSPEAR (thrombospondin type laminin G domain and EAR repeats, HGNC:1268) is a protein-coding gene on chromosome 21q22.3, encoding Thrombospondin-type laminin G domain and EAR repeat-containing protein (Q8WU66). Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 54084 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 526 total — 47 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 17
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_144991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1268
Approved symbol	TSPEAR
Name	thrombospondin type laminin G domain and EAR repeats
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC11251, TSP-EAR
Ensembl gene	ENSG00000175894
Ensembl biotype	protein_coding
OMIM	612920
Entrez	54084

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000323084, ENST00000397916, ENST00000642437, ENST00000943283

RefSeq mRNA: 2 — MANE Select: NM_144991 NM_001272037, NM_144991

CCDS: CCDS13712

Canonical transcript exons

ENST00000323084 — 12 exons

Exon	Start	End
ENSE00001283944	44525653	44525839
ENSE00001283963	44531043	44531133
ENSE00001283969	44504780	44504881
ENSE00001283979	44521883	44522112
ENSE00001283993	44527292	44527518
ENSE00001284001	44528452	44528583
ENSE00001284011	44529798	44529954
ENSE00001284021	44533685	44533923
ENSE00001284037	44509199	44509386
ENSE00003535905	44567785	44568005
ENSE00003826265	44711433	44711572
ENSE00003842452	44497893	44499936

Expression profiles

Bgee: expression breadth broad, 88 present calls, max score 62.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1080 / max 13.6209, expressed in 47 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190756	0.1080	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	62.65	gold quality
adenohypophysis	UBERON:0002196	62.11	gold quality
pituitary gland	UBERON:0000007	61.63	gold quality
right testis	UBERON:0004534	59.74	gold quality
left testis	UBERON:0004533	59.73	gold quality
apex of heart	UBERON:0002098	58.83	gold quality
myocardium	UBERON:0002349	58.23	gold quality
islet of Langerhans	UBERON:0000006	57.89	gold quality
testis	UBERON:0000473	57.75	gold quality
right lobe of liver	UBERON:0001114	57.71	gold quality
heart left ventricle	UBERON:0002084	57.64	gold quality
vena cava	UBERON:0004087	57.25	gold quality
tendon of biceps brachii	UBERON:0008188	57.22	gold quality
cardiac ventricle	UBERON:0002082	57.05	gold quality
left lobe of thyroid gland	UBERON:0001120	57.03	gold quality
thyroid gland	UBERON:0002046	56.59	gold quality
cortical plate	UBERON:0005343	56.42	gold quality
right lobe of thyroid gland	UBERON:0001119	56.06	gold quality
sperm	CL:0000019	55.47	gold quality
right atrium auricular region	UBERON:0006631	55.47	gold quality
cardiac atrium	UBERON:0002081	55.08	gold quality
lower lobe of lung	UBERON:0008949	54.80	silver quality
nasal cavity epithelium	UBERON:0005384	54.58	gold quality
heart	UBERON:0000948	53.28	gold quality
parotid gland	UBERON:0001831	52.24	gold quality
pancreas	UBERON:0001264	51.97	gold quality
oocyte	CL:0000023	51.60	gold quality
upper leg skin	UBERON:0004262	50.33	silver quality
substantia nigra pars compacta	UBERON:0001965	50.19	gold quality
lymph node	UBERON:0000029	49.73	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	21.70
E-ANND-3	no	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting TSPEAR, 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-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-1207-5P	99.49	69.11	2983

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 9)

• The TSPEAR/C21orf29 promoter is activated by Trichostatin A (TSA) treatment according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
• TSPEAR, cause disorders with auditory features: epilepsy, which can include auditory features in humans; audiogenic seizures in animals; and/or hearing impairments in humans and mice. (PMID:22678063)
• using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter (PMID:27736875)
• TSPEAR expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)
• TSPEAR mutation is associated with tooth agenesis. (PMID:30046887)
• Novel TSPEAR mutations in non-syndromic oligodontia. (PMID:32112661)
• TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study. (PMID:34042254)
• Confirmation of a Phenotypic Entity for TSPEAR Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity. (PMID:35741818)
• Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14. (PMID:37009414)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspeara	ENSDARG00000077580
danio_rerio	tspearb	ENSDARG00000089235
mus_musculus	Tspear	ENSMUSG00000069581
rattus_norvegicus	Tspear	ENSRNOG00000001219
drosophila_melanogaster	clos	FBGN0261016

Protein

Protein identifiers

Thrombospondin-type laminin G domain and EAR repeat-containing protein — Q8WU66 (reviewed: Q8WU66)

All UniProt accessions (2): Q8WU66, A0A2R8YFK6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway. May play a role in development or function of the auditory system.

Subcellular location. Secreted. Cell surface. Cell projection. Stereocilium.

Disease relevance. Deafness, autosomal recessive, 98 (DFNB98) [MIM:614861] A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Ectodermal dysplasia 14, hypohidrotic/hair/tooth/nail type (ECTD14) [MIM:618180] A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures such as teeth, hair, nails and sweat glands. ECTD14 is an autosomal recessive form characterized by scalp hypotrichosis, hypodontia, conical teeth, and variable facial dysmorphism. Some patients have dystrophic nails and decreased sweating. The disease is caused by variants affecting the gene represented in this entry. Tooth agenesis, selective, 10 (STHAG10) [MIM:620173] A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG10 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WU66-1	1	yes
Q8WU66-2	2

RefSeq proteins (2): NP_001258966, NP_659428* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005492	EPTP	Repeat
IPR009039	EAR	Repeat
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR048287	TSPN-like_N	Domain

Pfam: PF03736

UniProt features (34 total): sequence variant 17, repeat 7, glycosylation site 5, splice variant 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WU66-F1	87.47	0.65

Functional residue map

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

Glycosylation sites (5): 320, 468, 497, 556, 569

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): CREL_01, RORA1_01, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_CELL_SURFACE, GOBP_TOOTH_MINERALIZATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, RYTAAWNNNTGAY_UNKNOWN, TGANTCA_AP1_C, GOBP_MOLTING_CYCLE, GOBP_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GATA1_04, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, CART1_01, chr21q22

GO Biological Process (6): signal transduction (GO:0007165), Notch signaling pathway (GO:0007219), sensory perception of sound (GO:0007605), regulation of Notch signaling pathway (GO:0008593), hair cycle process (GO:0022405), tooth mineralization (GO:0034505)

GO Molecular Function (0):

GO Cellular Component (5): extracellular region (GO:0005576), cell surface (GO:0009986), stereocilium (GO:0032420), ciliary membrane (GO:0060170), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
sensory perception of mechanical stimulus	1
Notch signaling pathway	1
regulation of signal transduction	1
molting cycle process	1
hair cycle	1
biomineral tissue development	1
odontogenesis	1
stereocilium bundle	1
neuron projection	1
actin-based cell projection	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPEAR	PHETA1	Q8N4B1	665
TSPEAR	SMPX	Q9UHP9	665
TSPEAR	CUX2	O14529	649
TSPEAR	CEACAM16	Q2WEN9	614
TSPEAR	GPSM2	P81274	608
TSPEAR	TPRN	Q4KMQ1	595
TSPEAR	TRPM2	O94759	549
TSPEAR	OTOGL	Q3ZCN5	549
TSPEAR	SLC4A4	Q9Y6R1	548
TSPEAR	STRC	Q7RTU9	544
TSPEAR	KRTAP10-5	P60370	543
TSPEAR	ABCA13	Q86UQ4	521
TSPEAR	HDHD3	Q9BSH5	513
TSPEAR	KRTAP10-1	P60331	507
TSPEAR	KRTCAP3	Q53RY4	504

IntAct

2 interactions, top by confidence:

A	B	Type	Score
	VPS37C	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): TSPEAR (Two-hybrid)

ESM2 similar proteins: A2AA28, A2RRH5, A4FV42, A6NDL7, A7MCT6, B0K012, B2RYG8, D3YWP0, D3ZRW8, E1B8U2, J3S6Y1, P21964, P50747, Q0V8R7, Q1JP61, Q2TBI8, Q3SZD4, Q3U2J5, Q4VBE8, Q58DC7, Q5E9Y6, Q5RJL2, Q5VZV1, Q6DJF8, Q6GQ33, Q6P9U1, Q7Z624, Q80WC9, Q86XA0, Q8BNV1, Q8C436, Q8CDZ2, Q8IZ69, Q8N371, Q8R1C6, Q8WU66, Q920N2, Q96AZ1, Q96CB9, Q96RR1

Diamond homologs: J3S6Y1, Q8WU66, Q90827, A1A5Y0, A2RUV0, A2VCU8, A6QR11, B3EWY9, B5DFC9, G3I6Z6, O75095, O88322, P07996, P10493, P14585, P21783, P35441, P35448, P35555, P35556, P46531, P82279, P98133, Q01705, Q07008, Q14112, Q20911, Q28178, Q2PC93, Q2TAL6, Q2VWQ2, Q3U515, Q5R3Z7, Q5RBP1, Q61220, Q61554, Q61555, Q62918, Q62919, Q6AZ60

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	10
Uncertain significance	210
Likely benign	148
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1030229	NM_144991.3(TSPEAR):c.789T>G (p.Tyr263Ter)	Pathogenic
1188075	NM_144991.3(TSPEAR):c.1493del (p.Gly498fs)	Pathogenic
1311928	NM_144991.3(TSPEAR):c.430C>T (p.Arg144Ter)	Pathogenic
1348015	NC_000021.8:g.(?46131328)(46131429_?)del	Pathogenic
1412751	NC_000021.8:g.(?45919666)(45942015_?)del	Pathogenic
1801840	NM_144991.3(TSPEAR):c.1423G>C (p.Gly475Arg)	Pathogenic
1801842	NM_144991.3(TSPEAR):c.48del (p.Gly17fs)	Pathogenic
1806398	NM_144991.3(TSPEAR):c.1899dup (p.Thr634fs)	Pathogenic
1915967	NM_144991.3(TSPEAR):c.37del (p.Leu13fs)	Pathogenic
1925665	NM_144991.3(TSPEAR):c.178C>T (p.Gln60Ter)	Pathogenic
1942560	NM_144991.3(TSPEAR):c.1514C>A (p.Ser505Ter)	Pathogenic
1960364	NM_144991.3(TSPEAR):c.199dup (p.Arg67fs)	Pathogenic
2036464	NM_144991.3(TSPEAR):c.1202_1203del (p.Ser401fs)	Pathogenic
2081026	NM_144991.3(TSPEAR):c.1093C>T (p.Gln365Ter)	Pathogenic
2111094	NM_144991.3(TSPEAR):c.1442_1445del (p.Phe481fs)	Pathogenic
2111095	NM_144991.3(TSPEAR):c.1334_1336+45del	Pathogenic
2142905	NM_144991.3(TSPEAR):c.1246dup (p.Tyr416fs)	Pathogenic
2415153	NM_144991.3(TSPEAR):c.160del (p.His54fs)	Pathogenic
2419489	NM_144991.3(TSPEAR):c.1336+2T>A	Pathogenic
2427319	NC_000021.8:g.(?45945516)(45947421_?)del	Pathogenic
2663338	NM_144991.3(TSPEAR):c.1065del (p.Lys355fs)	Pathogenic
2793460	NM_144991.3(TSPEAR):c.277_278del (p.Leu93fs)	Pathogenic
2818748	NM_144991.3(TSPEAR):c.1336+1G>A	Pathogenic
2865945	NM_144991.3(TSPEAR):c.379C>T (p.Gln127Ter)	Pathogenic
2875832	NM_144991.3(TSPEAR):c.1217G>A (p.Trp406Ter)	Pathogenic
2883825	NM_144991.3(TSPEAR):c.1783G>T (p.Gly595Ter)	Pathogenic
2891535	NM_144991.3(TSPEAR):c.2T>C (p.Met1Thr)	Pathogenic
2981785	NM_144991.3(TSPEAR):c.540dup (p.Ile181fs)	Pathogenic
2986019	NM_144991.3(TSPEAR):c.98A>C (p.Asp33Ala)	Pathogenic
2986614	NM_144991.3(TSPEAR):c.1463C>A (p.Ser488Ter)	Pathogenic

SpliceAI

9170 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44509193:GCATA:G	donor_loss	1.0000
21:44509194:CATAC:C	donor_loss	1.0000
21:44509195:ATAC:A	donor_loss	1.0000
21:44509196:TA:T	donor_loss	1.0000
21:44509198:C:CT	donor_loss	1.0000
21:44527520:T:C	acceptor_gain	1.0000
21:44528449:CA:C	donor_loss	1.0000
21:44528450:A:C	donor_loss	1.0000
21:44528451:CCTGC:C	donor_loss	1.0000
21:44528581:TTT:T	acceptor_gain	1.0000
21:44528581:TTTC:T	acceptor_loss	1.0000
21:44528582:TT:T	acceptor_gain	1.0000
21:44528583:TC:T	acceptor_loss	1.0000
21:44528584:C:CC	acceptor_gain	1.0000
21:44528584:C:T	acceptor_loss	1.0000
21:44531037:A:AC	donor_gain	1.0000
21:44531038:C:CC	donor_gain	1.0000
21:44531132:TT:T	acceptor_gain	1.0000
21:44533683:A:AC	donor_gain	1.0000
21:44533684:C:CC	donor_gain	1.0000
21:44568006:C:CC	acceptor_gain	1.0000
21:44499933:CCAC:C	acceptor_gain	0.9900
21:44499934:CACC:C	acceptor_gain	0.9900
21:44499937:C:CC	acceptor_gain	0.9900
21:44499937:CT:C	acceptor_loss	0.9900
21:44499938:T:G	acceptor_loss	0.9900
21:44502585:C:CA	donor_gain	0.9900
21:44504774:CATTA:C	donor_loss	0.9900
21:44504776:TTA:T	donor_loss	0.9900
21:44504777:TAC:T	donor_loss	0.9900

AlphaMissense

4352 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44522090:A:C	S453R	0.999
21:44522090:A:T	S453R	0.999
21:44522092:T:G	S453R	0.999
21:44504791:A:C	S615R	0.998
21:44504791:A:T	S615R	0.998
21:44504793:T:G	S615R	0.998
21:44504871:A:G	W589R	0.998
21:44504871:A:T	W589R	0.998
21:44499916:A:G	F626S	0.997
21:44509334:A:G	L540P	0.996
21:44509368:A:G	W529R	0.996
21:44509368:A:T	W529R	0.996
21:44509265:G:A	S563F	0.995
21:44521980:A:G	L490P	0.995
21:44522014:A:G	W479R	0.995
21:44522014:A:T	W479R	0.995
21:44525710:A:G	W427R	0.995
21:44525710:A:T	W427R	0.995
21:44504879:G:T	A586D	0.994
21:44509331:G:T	A541D	0.994
21:44521971:G:T	A493D	0.994
21:44525751:A:G	F413S	0.994
21:44527318:A:G	W375R	0.994
21:44527318:A:T	W375R	0.994
21:44499875:A:G	W640R	0.993
21:44499875:A:T	W640R	0.993
21:44504784:A:C	Y618D	0.993
21:44504828:G:T	A603D	0.993
21:44525676:A:G	L438P	0.993
21:44525718:G:T	A424D	0.993

dbSNP variants (sampled 300 via entrez): RS1000017833 (21:44623532 C>T), RS1000020355 (21:44505647 T>C), RS1000067603 (21:44649147 C>G,T), RS1000118881 (21:44691234 C>T), RS1000122245 (21:44636283 T>C), RS1000122414 (21:44520629 C>T), RS1000174785 (21:44553115 G>A), RS1000184028 (21:44515096 C>T), RS1000201871 (21:44625788 G>A,T), RS1000206405 (21:44592790 C>G,T), RS1000233087 (21:44709255 C>T), RS1000248517 (21:44565890 C>T), RS1000263362 (21:44548081 T>C), RS1000316461 (21:44547705 G>T), RS1000350670 (21:44639201 C>A,T)

Disease associations

OMIM: gene MIM:612920 | disease phenotypes: MIM:618180, MIM:620173, MIM:614861, MIM:305100

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis	Strong	Autosomal recessive
tooth agenesis, selective, 10	Strong	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 98	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Disputed	AR

Mondo (6): ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (MONDO:0032584), tooth agenesis, selective, 10 (MONDO:0859339), autosomal recessive nonsyndromic hearing loss 98 (MONDO:0013929), hearing loss disorder (MONDO:0005365), ectodermal dysplasia syndrome (MONDO:0019287), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (3): Hypodontia-scalp hypotrichosis-facial dysmorphism syndrome (Orphanet:685067), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Ectodermal dysplasia syndrome (Orphanet:79373)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000300	Oval face
HP:0000341	Narrow forehead
HP:0000364	Hearing abnormality
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000494	Downslanted palpebral fissures
HP:0000668	Hypodontia
HP:0000677	Oligodontia
HP:0000698	Conical tooth
HP:0000966	Hypohidrosis
HP:0002209	Sparse scalp hair
HP:0003577	Congenital onset
HP:0010763	Low insertion of columella
HP:0012471	Thick vermilion border

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002970_3	Corticobasal degeneration	4.000000e-06
GCST004793_1	Amyotrophic lateral sclerosis in C9orf72 mutation negative individuals	2.000000e-07
GCST006661_335	Male-pattern baldness	5.000000e-08
GCST007672_12	3-month functional outcome in ischaemic stroke (modified Rankin score)	2.000000e-06
GCST009267_16	Dental caries (decayed, missing and filled teeth)	4.000000e-06
GCST012279_16	Suicide attempt severity in mood disorders	1.000000e-05
GCST012280_8	Suicidality in mood disorders	1.000000e-05

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0006882	suicide behaviour measurement

MeSH disease descriptors (3)

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
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C564609	Deafness, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs201441480	Efficacy	3	aspirin;clopidogrel	Acute coronary syndrome;Major Adverse Cardiac Events (MACE)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs201441480	KRTAP10-4, TSPEAR	3	3.50	1	aspirin;clopidogrel

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases expression, increases methylation	3
Benzo(a)pyrene	affects methylation	2
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation, decreases methylation	1
indeno(1,2,3-cd)pyrene	increases expression	1
picene	increases expression	1
Acetaminophen	increases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	increases methylation	1
Pesticides	affects methylation	1
Tetrachlorodibenzodioxin	increases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases methylation	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_2150	OCI-M2	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss