DSG4

Summary

DSG4 (desmoglein 4, HGNC:21307) is a protein-coding gene on chromosome 18q12.1, encoding Desmoglein-4 (Q86SJ6). A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth.

Source: NCBI Gene 147409 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotrichosis 6 (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 53 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 24
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_177986

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21307
Approved symbol	DSG4
Name	desmoglein 4
Location	18q12.1
Locus type	gene with protein product
Status	Approved
Aliases	CDHF13, LAH
Ensembl gene	ENSG00000175065
Ensembl biotype	protein_coding
OMIM	607892
Entrez	147409

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000308128, ENST00000359747

RefSeq mRNA: 2 — MANE Select: NM_177986 NM_001134453, NM_177986

CCDS: CCDS11897, CCDS45845

Canonical transcript exons

ENST00000308128 — 16 exons

Exon	Start	End
ENSE00001199162	31411231	31411448
ENSE00001333194	31409745	31409808
ENSE00001333196	31409452	31409591
ENSE00001333199	31406077	31406373
ENSE00001333202	31403416	31403634
ENSE00001333204	31400881	31401020
ENSE00001333206	31399272	31399543
ENSE00001333208	31392155	31392340
ENSE00001333212	31391078	31391212
ENSE00001333216	31390656	31390822
ENSE00001333219	31388874	31389018
ENSE00001333222	31388367	31388522
ENSE00001333224	31386688	31386819
ENSE00001333225	31385136	31385171
ENSE00001402593	31376777	31376959
ENSE00001414221	31412828	31414909

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 79.16.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.16	silver quality
esophagus mucosa	UBERON:0002469	51.45	gold quality
lower lobe of lung	UBERON:0008949	48.96	silver quality
lower esophagus mucosa	UBERON:0035834	46.56	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	46.43	gold quality
duodenum	UBERON:0002114	45.82	gold quality
skin of abdomen	UBERON:0001416	45.70	gold quality
rectum	UBERON:0001052	43.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
vagina	UBERON:0000996	43.13	gold quality
zone of skin	UBERON:0000014	43.09	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
bone marrow cell	CL:0002092	41.73	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
skin of leg	UBERON:0001511	41.12	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
skin of hip	UBERON:0001554	40.09	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXN1, HOXC13, LEF1, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5

miRNA regulators (miRDB)

32 targeting DSG4, 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-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-106A-5P	99.90	73.94	2683
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-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-4698	99.84	71.41	4303
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-5579-5P	96.32	68.54	730

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 13)

• the human desmoglein 4 gene (DSG4) demonstrates that it is composed of 16 exons spanning approximately 37 kb of 18q12 and is situated between DSG1 and DSG3. (PMID:12648213)
• The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis, as well as in the lanceolate hair mouse. We also show that DSG4 is an autoantigen in pemphigus vulgaris. (PMID:12705872)
• DSG4 is pathogenic in pemphigus and staphylococcal scalded skin syndrome. (PMID:15545999)
• A large, intragenic deletion in the desmoglein 4 gene (DSG4) is the underlying mutation in an autosomal recessive form of hypotrichosis. (PMID:16382669)
• The DSG4 protein is expressed in the more highly differentiated layers of the epidermis. (PMID:16533311)
• Epitopes of Dsg4 may play a role in the pathogenesis of pemphigus vulgaris . (PMID:17294735)
• identification of a single nucleotide deletion within exon 3 of DSG4, designated 87delG in a Pakistani family with localized autosomal recessive hypotrichosis; this results in a frameshift and premature termination codon 162 bp downstream of the deletion (PMID:17392831)
• show that HOXC13, LEF1 and FOXN1 repress DSG4 transcription and provide in vitro and in vivo evidence correlating the Notch pathway with the activation and/or maintenance of DSG4 expression in the hair follicle. (PMID:19683850)
• Genetic analysis of striate palmoplantar keratoderma and hypotrichosis identified their responsible genes as desmogleins 1 and 4, respectively. (PMID:22189787)
• This study further extends the body of evidence that mutations in the DSG4 gene result in both hypotrichosis and monilethrix-like scalp hair. (PMID:25251037)
• Case Report: autosomal recessive keratosis pilaris atrophicans caused by mutation in DSG4. (PMID:29796690)
• Desmoglein-4 Deficiency Exacerbates Psoriasiform Dermatitis in Rats While Psoriasis Patients Displayed a Decreased Gene Expression of DSG4. (PMID:33995349)
• Autosomal recessive monilethrix: Novel variants of the DSG4 gene in three Chinese families. (PMID:35146972)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dsg4	ENSMUSG00000001804
rattus_norvegicus	Dsg4	ENSRNOG00000022364

Paralogs (6): DSG2 (ENSG00000046604), DSC2 (ENSG00000134755), DSG3 (ENSG00000134757), DSG1 (ENSG00000134760), DSC3 (ENSG00000134762), DSC1 (ENSG00000134765)

Protein

Protein identifiers

Desmoglein-4 — Q86SJ6 (reviewed: Q86SJ6)

Alternative names: Cadherin family member 13

All UniProt accessions (1): Q86SJ6

UniProt curated annotations — full annotation on UniProt →

Function. A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. Coordinates the transition from proliferation to differentiation in hair follicle keratinocytes. Plays a role in moderating lymphocyte migration to inflamed skin and maintaining homeostasis of the epidermal inflammatory response.

Subunit / interactions. Interacts with JUP.

Subcellular location. Cell membrane. Cell junction. Desmosome.

Tissue specificity. In scalp follicles, present in the inner root sheath (IRS) and all layers of the matrix and precortex (at protein level). Expressed in the brain, muscle, kidney, pancreas, spleen, thymus and weakly expressed in the lung, liver, heart and placenta. Highly expressed in skin, testis and prostate; less in salivary gland.

Disease relevance. Hypotrichosis 6 (HYPT6) [MIM:607903] A condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed. HYPT6 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Autoantibodies against DSG4 are found in patients with pemphigus vulgaris. Pemphigus vulgaris is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion.

Domain organisation. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86SJ6-1	1	yes
Q86SJ6-2	2

RefSeq proteins (2): NP_001127925, NP_817123* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000233	Cadherin_Y-type_LIR	Domain
IPR002126	Cadherin-like_dom	Domain
IPR009122	Desmosomal_cadherin	Family
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR027397	Catenin-bd_sf	Homologous_superfamily
IPR050971	Cadherin-domain_protein	Family

Pfam: PF00028, PF01049

UniProt features (23 total): sequence variant 8, domain 4, repeat 2, glycosylation site 2, topological domain 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SJ6-F1	65.63	0.33

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 (2): 110, 545

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope

MSigDB gene sets: 100 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GGGTGGRR_PAX4_03, NKX61_01, GOBP_CELL_CELL_ADHESION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, chr18q12, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, GATA1_03, GOBP_RESPONSE_TO_BMP, AFP1_Q6, GOBP_RESPONSE_TO_GROWTH_FACTOR, LEF1_Q6, GATA4_Q3

GO Biological Process (6): hair follicle development (GO:0001942), homophilic cell-cell adhesion (GO:0007156), keratinocyte differentiation (GO:0030216), BMP signaling pathway (GO:0030509), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (2): calcium ion binding (GO:0005509), metal ion binding (GO:0046872)

GO Cellular Component (5): cornified envelope (GO:0001533), plasma membrane (GO:0005886), desmosome (GO:0030057), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
cell-cell adhesion	1
epidermal cell differentiation	1
skin development	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell adhesion	1
cellular process	1
metal ion binding	1
cation binding	1
plasma membrane	1
membrane	1
cell periphery	1
cell-cell junction	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DSG4	KRT83	P78385	887
DSG4	KRT86	P78387	844
DSG4	LPAR6	P43657	758
DSG4	KRT81	Q14533	738
DSG4	CDSN	Q15517	688
DSG4	TGM5	O43548	667
DSG4	PKP1	Q13835	598
DSG4	DSP	P15924	577
DSG4	LIPH	Q8WWY8	572
DSG4	HOXC13	P31276	550
DSG4	SNRPE	P08578	497
DSG4	PKP3	Q9Y446	491
DSG4	CDH17	Q12864	486
DSG4	EPS8L3	Q8TE67	482
DSG4	ACP4	Q9BZG2	460

IntAct

113 interactions, top by confidence:

A	B	Type	Score
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
RAC1	COX6C	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
OSBPL8	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
PMM1	PMM2	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
RPN2	SMPD2	psi-mi:“MI:0914”(association)	0.530
CPLX3	CIAO1	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
OR51E2	DUSP14	psi-mi:“MI:0914”(association)	0.530
LACC1	DUSP14	psi-mi:“MI:0914”(association)	0.530
CFAP210	DUSP14	psi-mi:“MI:0914”(association)	0.530
SYT16	DUSP14	psi-mi:“MI:0914”(association)	0.530
LPCAT4	DUSP14	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
NSMAF	DUSP14	psi-mi:“MI:0914”(association)	0.530
TFG	CRYAB	psi-mi:“MI:0914”(association)	0.530
ELMOD1	LDHC	psi-mi:“MI:0914”(association)	0.530
DOLPP1	VSIG8	psi-mi:“MI:0914”(association)	0.530
APIP	VSIG8	psi-mi:“MI:0914”(association)	0.530
C1R	BIRC2	psi-mi:“MI:0914”(association)	0.530
HERC3	H3-7	psi-mi:“MI:0914”(association)	0.530
FNTB	YKT6	psi-mi:“MI:0914”(association)	0.530
SKA2	VSIG8	psi-mi:“MI:0914”(association)	0.530

BioGRID (161): DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DSG4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4GGP7, B1Q236, B8V7Q1, B8VIW9, F1QSQ0, F8W3X3, G5EDK5, H2A0L8, O02466, O15943, O44386, O44730, P28827, P34616, P35822, P55289, P70408, Q02763, Q02858, Q03600, Q03763, Q06807, Q09165, Q15262, Q19319, Q24247, Q24298, Q5RJH3, Q60ZN5, Q61495, Q68SP4, Q6W3B0, Q7TMD7, Q7TSF0, Q7TSF1, Q86SJ6, Q86WI1, Q8JHW2, Q8VHN7, Q8WXG9

Diamond homologs: A0A8M2BIB6, B0KW95, B2KI42, B4USZ0, F1PAA9, H2EQR6, O18926, O35902, O55075, O55111, O88277, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P19535, P20310, P22223, P24503, P30944, P32926, P33145, P33146, P33147, P33148, P33150, P33152, P33545, P39038, P55283, P55290, P55291, P55292, P55849, P55850, P79883

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FOXN1	“down-regulates quantity by repression”	DSG4	“transcriptional regulation”
LEF1	“down-regulates quantity by repression”	DSG4	“transcriptional regulation”
HOXC13	“down-regulates quantity by repression”	DSG4	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
anterograde axonal transport	5	18.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	29
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2721	NM_177986.5(DSG4):c.574T>C (p.Ser192Pro)	Pathogenic
2722	NM_177986.5(DSG4):c.2038dup (p.Ser680fs)	Pathogenic
2723	NM_177986.5(DSG4):c.216+1G>T	Pathogenic
2725	NM_177986.5(DSG4):c.763del (p.Cys255fs)	Pathogenic
3391063	NM_177986.5(DSG4):c.2389C>T (p.Arg797Ter)	Likely pathogenic
3777044	NM_177986.5(DSG4):c.1576T>C (p.Phe526Leu)	Likely pathogenic

SpliceAI

1357 predictions. Top by Δscore:

Variant	Effect	Δscore
18:31376957:ATGG:A	donor_loss	1.0000
18:31376958:TGGT:T	donor_loss	1.0000
18:31376959:GGTA:G	donor_loss	1.0000
18:31376961:T:A	donor_loss	1.0000
18:31386816:CAAAG:C	donor_loss	1.0000
18:31386817:AAAGT:A	donor_loss	1.0000
18:31386819:AG:A	donor_loss	1.0000
18:31386820:GTAA:G	donor_loss	1.0000
18:31388364:TA:T	acceptor_loss	1.0000
18:31388365:A:AC	acceptor_loss	1.0000
18:31388365:A:AG	acceptor_gain	1.0000
18:31388366:G:GG	acceptor_gain	1.0000
18:31388366:GATTC:G	acceptor_gain	1.0000
18:31388519:CTTG:C	donor_gain	1.0000
18:31388519:CTTGG:C	donor_loss	1.0000
18:31388520:TTGGT:T	donor_loss	1.0000
18:31388521:TG:T	donor_gain	1.0000
18:31388521:TGG:T	donor_loss	1.0000
18:31388522:GG:G	donor_gain	1.0000
18:31388522:GGTA:G	donor_loss	1.0000
18:31388523:G:GG	donor_gain	1.0000
18:31388523:GTA:G	donor_loss	1.0000
18:31388524:TAA:T	donor_loss	1.0000
18:31388868:CCACA:C	acceptor_loss	1.0000
18:31388869:CACAG:C	acceptor_loss	1.0000
18:31388870:ACAGA:A	acceptor_loss	1.0000
18:31388871:CA:C	acceptor_loss	1.0000
18:31388872:AGA:A	acceptor_loss	1.0000
18:31388873:G:A	acceptor_loss	1.0000
18:31389015:GCCA:G	donor_gain	1.0000

AlphaMissense

6853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:31388449:T:C	F100S	1.000
18:31388935:T:A	V145D	1.000
18:31388941:T:A	V147D	1.000
18:31386814:G:C	A71P	0.999
18:31386815:C:A	A71D	0.999
18:31388403:T:G	Y85D	0.999
18:31388421:G:A	G91R	0.999
18:31388421:G:C	G91R	0.999
18:31388422:G:A	G91E	0.999
18:31388448:T:C	F100L	0.999
18:31388449:T:G	F100C	0.999
18:31388450:C:A	F100L	0.999
18:31388450:C:G	F100L	0.999
18:31388469:G:T	G107W	0.999
18:31388470:G:A	G107E	0.999
18:31388470:G:T	G107V	0.999
18:31388476:T:G	I109S	0.999
18:31388500:G:C	R117T	0.999
18:31388500:G:T	R117I	0.999
18:31388501:A:C	R117S	0.999
18:31388501:A:T	R117S	0.999
18:31388518:T:C	F123S	0.999
18:31388882:C:G	C127W	0.999
18:31388929:T:C	L143P	0.999
18:31388946:G:C	D149H	0.999
18:31388954:T:A	N151K	0.999
18:31388954:T:G	N151K	0.999
18:31388956:A:C	D152A	0.999
18:31388956:A:T	D152V	0.999
18:31388965:C:A	P155Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000171832 (18:31397198 A>T), RS1000203592 (18:31375628 A>T), RS1000233696 (18:31394295 C>T), RS1000492565 (18:31378928 G>C,T), RS1000512496 (18:31396078 G>A), RS1000518413 (18:31381000 G>A), RS1000567146 (18:31401812 T>A), RS1000646723 (18:31395779 T>A,G), RS1000687673 (18:31390043 T>A), RS1001058845 (18:31407460 C>T), RS1001204927 (18:31379470 A>G), RS1001230540 (18:31389763 G>A,C), RS1001355996 (18:31409203 A>T), RS1001457891 (18:31401970 A>T), RS1001542677 (18:31403165 G>C)

Disease associations

OMIM: gene MIM:607892 | disease phenotypes: MIM:607903

GenCC curated gene-disease

Disease	Classification	Inheritance
hypotrichosis 6	Definitive	Autosomal recessive
hypotrichosis simplex	Supportive	Autosomal dominant
monilethrix	Supportive	Autosomal dominant

Mondo (3): hypotrichosis 6 (MONDO:0011932), hypotrichosis simplex (MONDO:0018914), monilethrix (MONDO:0008009)

Orphanet (1): Hypotrichosis simplex (Orphanet:55654)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000499	Abnormal eyelash morphology
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000653	Sparse eyelashes
HP:0000989	Pruritus
HP:0001249	Intellectual disability
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0002209	Sparse scalp hair
HP:0002213	Fine hair
HP:0002217	Slow-growing hair
HP:0002231	Sparse body hair
HP:0002232	Patchy alopecia
HP:0002299	Brittle hair
HP:0003577	Congenital onset
HP:0003777	Pili torti
HP:0007502	Follicular hyperkeratosis
HP:0008070	Sparse hair
HP:0010783	Erythema
HP:0045075	Sparse eyebrow
HP:0100543	Cognitive impairment
HP:0100753	Schizophrenia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D056734	Monilethrix	C16.131.077.592; C16.320.850.647; C17.800.329.984; C17.800.827.602
C537160	Hypotrichosis simplex (supp.)
C564312	Hypotrichosis, Localized, Autosomal Recessive 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tungsten carbide	affects binding, decreases expression	1
urushiol	increases expression	1
sodium arsenite	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Cadmium	decreases expression, increases abundance	1
Cobalt	affects binding, decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases expression, affects cotreatment	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03492866	PHASE2	UNKNOWN	Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN