CST6

Summary

CST6 (cystatin E/M, HGNC:2478) is a protein-coding gene on chromosome 11q13.1, encoding Cystatin-M (Q15828). High affinity inhibitor for cathepsin L, cathepsin L2 (cathepsin V), and legumain.

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. This gene encodes a cystatin from the type 2 family, which is down-regulated in metastatic breast tumor cells as compared to primary tumor cells. Loss of expression is likely associated with the progression of a primary tumor to a metastatic phenotype.

Source: NCBI Gene 1474 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia 15, hypohidrotic/hair type (Strong, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 30 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_001323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2478
Approved symbol	CST6
Name	cystatin E/M
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175315
Ensembl biotype	protein_coding
OMIM	601891
Entrez	1474

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000312134

RefSeq mRNA: 1 — MANE Select: NM_001323 NM_001323

CCDS: CCDS8126

Canonical transcript exons

ENST00000312134 — 3 exons

Exon	Start	End
ENSE00001189935	66013317	66013505
ENSE00001189942	66012826	66012951
ENSE00001189949	66012008	66012284

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 99.77.

FANTOM5 (CAGE): breadth broad, TPM avg 11.1415 / max 3078.4952, expressed in 646 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115272	10.6469	620
115266	0.2328	62
115268	0.0973	33
115267	0.0570	26
115269	0.0366	16
115271	0.0332	18
115270	0.0260	15
115273	0.0117	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.77	gold quality
upper leg skin	UBERON:0004262	99.67	gold quality
skin of abdomen	UBERON:0001416	99.22	gold quality
mammalian vulva	UBERON:0000997	99.10	gold quality
nipple	UBERON:0002030	99.09	gold quality
zone of skin	UBERON:0000014	98.68	gold quality
skin of leg	UBERON:0001511	98.38	gold quality
skin of hip	UBERON:0001554	97.76	gold quality
hair follicle	UBERON:0002073	96.83	gold quality
lower esophagus mucosa	UBERON:0035834	95.50	gold quality
right uterine tube	UBERON:0001302	94.99	gold quality
descending thoracic aorta	UBERON:0002345	94.25	gold quality
penis	UBERON:0000989	94.18	gold quality
amniotic fluid	UBERON:0000173	92.07	gold quality
thoracic aorta	UBERON:0001515	91.38	gold quality
ascending aorta	UBERON:0001496	91.30	gold quality
right lung	UBERON:0002167	89.12	gold quality
esophagus mucosa	UBERON:0002469	87.94	gold quality
cervix squamous epithelium	UBERON:0006922	87.48	silver quality
cervix epithelium	UBERON:0004801	87.28	gold quality
left lobe of thyroid gland	UBERON:0001120	86.47	gold quality
upper lobe of left lung	UBERON:0008952	86.29	gold quality
right coronary artery	UBERON:0001625	85.82	gold quality
right lobe of thyroid gland	UBERON:0001119	85.71	gold quality
buccal mucosa cell	CL:0002336	85.67	gold quality
upper lobe of lung	UBERON:0008948	85.52	gold quality
aorta	UBERON:0000947	85.35	gold quality
periodontal ligament	UBERON:0008266	84.81	gold quality
thyroid gland	UBERON:0002046	84.44	gold quality
oral cavity	UBERON:0000167	81.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	758.70
E-ANND-3	yes	9.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting CST6, 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-542-3P	99.34	67.58	1270
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-758-3P	98.42	68.60	1122

Literature-anchored findings (GeneRIF, showing 31)

• CST6 is not a major gene contributing to type 1 and 2 harlequin ichthyosis (PMID:12839564)
• Cystatin M suppresses the malignant phenotype of MDA-MB-435S cells. (PMID:14676833)
• Complete loss of expression of cystatin M was observed in two of three stage IV breast cancer patients. Immunohistochemical studies confirmed that expression of cystatin M in IDCs was partially or completely lost. (PMID:15466187)
• This study thus provides the first evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression. (PMID:16356477)
• Identification of CTSV & CTSL as targets for cystatin M/E, their (co)-expression in the stratum granulosum of skin, and activity of CTSL toward transglutaminase 3 strongly imply an important role for them in the differentiation process of human epidermis. (PMID:16565075)
• Tumors displaying CST6 gene methylation, display methylation in both ductal carcinoma in situ and invasive breast carcinoma lesions and reduced expression of cystatin M in these tumors was confirmed by immunohistochemistry (PMID:16912163)
• strong link between CST6 promoter hypermethylation and loss of CST6 expression in breast cancer cell lines (PMID:17043665)
• Cystatin M may encode a novel epigenetically inactivated candidate tumor suppressor gene. (PMID:17099723)
• Methylation-dependent epigenetic silencing of CST6 represents an important mechanism for loss of CST6 during breast tumorigenesis and/or progression to metastasis. (PMID:17540367)
• cystatin E/M is a cervical cancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation. (PMID:18506750)
• results demonstrate that epigenetic silencing of CST6 is frequent in adult and pediatric brain tumors and occurs in TICs, which are thought to give rise to the tumor (PMID:18607344)
• CST6, CXCL14, DHRS3, and SPP1 are regulated by BRAF signaling and may play a role in papillary thyroid carcinoma pathogenesis (PMID:18676742)
• These findings imply that CST6 is likely to involve in the proliferation and survival of pancreatic cancer probably through its proteinase inhibitory activity, and it is a promising molecular target for development of new therapeutic strategies for PDAC (PMID:18754876)
• The cysteine protease inhibitor cystatin M/E is a key regulator of a biochemical pathway that leads to epidermal terminal differentiation. (PMID:19005484)
• Cystatin M (CST6) tumor suppressor gene is concurrently down-regulated with other loci in breast epithelial cells cocultured with cancer-associated fibroblasts. (PMID:19074894)
• cystatin M/E has a role in skin barrier formation and a potential role as a tumor suppressor gene [review] (PMID:19262604)
• Results suggest that the downregulation of the CST6 gene is associated with promoter histone modifications and that this association plays an important role in prostate cancer progression during the invasive and metastatic stages of the disease. (PMID:19503093)
• Methylation of cystatin M promoter is associated with breast cancer. (PMID:19551853)
• the level of cystatin E/M regulates legumain activity and hence the invasive potential of human melanoma cells (PMID:20074384)
• An association between the quantity of CST6 methylation and the expression statuses of estrogen receptor, progesterone receptor, and HER4 in tumor tissues was found (PMID:21092257)
• The ectopic expression of CST6 in cancer cells rescued mice from overt osteolytic metastasis and deaths in the animal study, while CST6 knockdown markedly enhanced cancer cell bone metastasis and shortened animal survival. (PMID:22688893)
• Data show a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity. (PMID:22902879)
• The CST6 promoter is highly methylated in circulating cell-free DNA of breast cancer patients, but not in healthy individuals. (PMID:23006792)
• Developed a Methylation-Sensitive High Resolution Melting Analysis (MS-HRMA) assay for the investigation of CST6 promoter methylation in breast cancer patients.CST6 promoter was methylated in 39/80 of FFPEs. (PMID:23088560)
• Low CST6 expression is associated with breast cancer. (PMID:24742492)
• Results provide evidence that cystatin E/M is a tumor suppressor gene which plays an important role in the regulation of NF-kappaB. (PMID:27090639)
• Data suggest that melanoma cells internalize/absorb cystatin C from culture media, leading to increased intracellular cystatin C levels; cystatin E/M is internalized as well but at modest rate due to down-regulation of cell migration; however, the effect of intracellular cystatin E/M on down-regulation of legumain activity is pronounced. (PMID:28630039)
• High CST6 expression is associated with lymph-node metastasis in Triple-Negative Breast Cancer. (PMID:29530995)
• a loss-of-function variant in the human CST6 gene, which causes a novel autosomal recessive hypotrichosis syndrome (PMID:30425301)
• CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis. (PMID:34815788)
• CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation. (PMID:35881476)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cst6	ENSMUSG00000024846
rattus_norvegicus	Cst6	ENSRNOG00000020455
caenorhabditis_elegans		WBGENE00000534
caenorhabditis_elegans		WBGENE00000535
caenorhabditis_elegans		WBGENE00023486

Paralogs (11): CST7 (ENSG00000077984), CST9L (ENSG00000101435), CST3 (ENSG00000101439), CST4 (ENSG00000101441), CST8 (ENSG00000125815), CSTL1 (ENSG00000125823), CST11 (ENSG00000125831), CST5 (ENSG00000170367), CST2 (ENSG00000170369), CST1 (ENSG00000170373), CST9 (ENSG00000173335)

Protein

Protein identifiers

Cystatin-M — Q15828 (reviewed: Q15828)

Alternative names: Cystatin-6, Cystatin-E

All UniProt accessions (1): Q15828

UniProt curated annotations — full annotation on UniProt →

Function. High affinity inhibitor for cathepsin L, cathepsin L2 (cathepsin V), and legumain. Involved in the regulation of epidermal cornification, and hair follicle morphogenesis and maintenance.

Subcellular location. Secreted.

Tissue specificity. Restricted to the stratum granulosum of normal skin, the stratum granulosum/spinosum of psoriatic skin, and the secretory coils of eccrine sweat glands. Low expression levels are found in the nasal cavity.

Post-translational modifications. Substrate for transglutaminases. Acts as an acyl acceptor but not as an acyl donor.

Disease relevance. Ectodermal dysplasia 15, hypohidrotic/hair type (ECTD15) [MIM:618535] A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD15 is an autosomal recessive form characterized by hypotrichosis and absence of sweating except with extreme exercise. Skin is dry from birth and eczematous lesions may develop in adulthood. Other features include blepharitis and photophobia. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the cystatin family.

RefSeq proteins (1): NP_001314* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000010	Cystatin_dom	Domain
IPR018073	Prot_inh_cystat_CS	Conserved_site
IPR046350	Cystatin_sf	Homologous_superfamily

Pfam: PF00031

UniProt features (17 total): strand 4, helix 4, disulfide bond 2, signal peptide 1, chain 1, turn 1, short sequence motif 1, site 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4N6O	X-RAY DIFFRACTION	1.8
4N6N	X-RAY DIFFRACTION	1.87
4N6L	X-RAY DIFFRACTION	1.95
4N6M	X-RAY DIFFRACTION	2.9
6FK0	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15828-F1	90.46	0.73

Functional residue map

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

Catalytic / active sites (1): 36 (reactive site)

Disulfide bonds (2): 98–113, 126–146

Glycosylation sites (1): 137

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): JAEGER_METASTASIS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, chr11q13, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, TGANTCA_AP1_C, GOBP_EPIDERMIS_DEVELOPMENT, SAGIV_CD24_TARGETS_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, CAIRO_LIVER_DEVELOPMENT_UP, KARAKAS_TGFB1_SIGNALING, GOCC_CORNIFIED_ENVELOPE, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, STEIN_ESRRA_TARGETS_DN, GOMF_ENZYME_INHIBITOR_ACTIVITY

GO Biological Process (2): epidermis development (GO:0008544), anatomical structure morphogenesis (GO:0009653)

GO Molecular Function (3): cysteine-type endopeptidase inhibitor activity (GO:0004869), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (3): cornified envelope (GO:0001533), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue development	1
developmental process	1
anatomical structure development	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
plasma membrane	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CST6	LGMN	Q99538	954
CST6	TGM3	Q08188	866
CST6	ABCA12	Q86UK0	813
CST6	LORICRIN	P23490	784
CST6	CTSS	P25774	743
CST6	BRMS1	Q9HCU9	506
CST6	CST9	Q5W186	502
CST6	BRMS1L	Q5PSV4	479
CST6	FLG2	Q5D862	477
CST6	CTSL	P07711	460
CST6	CTSB	P07858	442
CST6	RASSF1	Q9NS23	432
CST6	CSTA	P01040	401
CST6	GSTP1	P09211	400
CST6	FLG	P20930	389

IntAct

83 interactions, top by confidence:

A	B	Type	Score
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
C9	APOE	psi-mi:“MI:0914”(association)	0.560
YIF1A	CST6	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN12	A2ML1	psi-mi:“MI:0914”(association)	0.530
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
CA8	IGLL5	psi-mi:“MI:0914”(association)	0.530
ZDHHC23	GAPDHS	psi-mi:“MI:0914”(association)	0.530
DNAAF19	KLK10	psi-mi:“MI:0914”(association)	0.530
CLEC5A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
MMRN1	CTSV	psi-mi:“MI:0914”(association)	0.530
B3GALNT1	DUSP14	psi-mi:“MI:0914”(association)	0.530
CST6	CTSV	psi-mi:“MI:0914”(association)	0.530
CERKL	PPM1B	psi-mi:“MI:0914”(association)	0.530
DHDH	ATRN	psi-mi:“MI:0914”(association)	0.530
LGMN	CST6	psi-mi:“MI:0570”(protein cleavage)	0.440
ANXA11	CST6	psi-mi:“MI:0915”(physical association)	0.400
PLEKHB2	CST6	psi-mi:“MI:0915”(physical association)	0.400
GSK3B	CST6	psi-mi:“MI:0915”(physical association)	0.370
BCAR3	CST6	psi-mi:“MI:0915”(physical association)	0.370
NOTCH2	CST6	psi-mi:“MI:0915”(physical association)	0.370
PALB2	CST6	psi-mi:“MI:0915”(physical association)	0.370
CST6	RAD51	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (103): CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Affinity Capture-MS), CST6 (Two-hybrid), CST6 (Two-hybrid), CST6 (Two-hybrid), CST6 (Two-hybrid), CST6 (Two-hybrid)

ESM2 similar proteins: A0A0K0IP23, A0A1S3PBB7, A0A224AHH8, A0A3S6I186, A0A5C1J0Z8, A0A6B9KZ52, A1L015, A1L017, B1P1J3, B2Z450, B7PKZ1, B7PKZ2, D0NBV1, D0NBV4, E3P6N5, E3P6N6, E3P6N7, E3P6N9, E3P6P0, E3P6P1, E3P6P2, E3P6P4, J3RYX9, O60676, O88969, P01048, P08932, P08935, P0DXA0, P19313, P22085, P23779, P28325, P32766, P35481, P81714, P90698, Q15828, Q2XXN5, Q331K1

Diamond homologs: A0A0K0IP23, B1P1J3, E3P6N3, E3P6N4, E3P6N5, E3P6N6, E3P6N7, E3P6N8, E3P6N9, E3P6P0, E3P6P1, E3P6P2, E3P6P3, E3P6P4, J3RYX9, O19092, O19093, O97862, P01035, P01038, P08935, P0DXA0, P22085, P81061, P81714, P90698, Q15828, Q2XXN5, Q6T6T4, Q7M429, Q91195, B2Z450, J3SE80, O89098, P01034, P14841, P19313, P21460, P35481, Q80ZN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	22
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
666253	NM_001323.4(CST6):c.361C>T (p.Gln121Ter)	Pathogenic
4845922	NM_001323.4(CST6):c.295del (p.Arg99fs)	Likely pathogenic

SpliceAI

215 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66012280:GCCAG:G	donor_gain	1.0000
11:66012281:CCAGG:C	donor_loss	1.0000
11:66012282:CAGGT:C	donor_loss	1.0000
11:66012285:GTGC:G	donor_loss	1.0000
11:66012286:T:A	donor_loss	1.0000
11:66012824:A:AG	acceptor_gain	1.0000
11:66012824:AGCT:A	acceptor_gain	1.0000
11:66012825:G:GG	acceptor_gain	1.0000
11:66012825:GCT:G	acceptor_gain	1.0000
11:66012825:GCTG:G	acceptor_gain	1.0000
11:66012949:G:GT	donor_gain	1.0000
11:66012817:T:G	acceptor_gain	0.9900
11:66012820:CCCCA:C	acceptor_loss	0.9900
11:66012821:CCCAG:C	acceptor_loss	0.9900
11:66012822:CCAGC:C	acceptor_loss	0.9900
11:66012823:CAGCT:C	acceptor_loss	0.9900
11:66012824:A:G	acceptor_loss	0.9900
11:66012824:AGCTG:A	acceptor_gain	0.9900
11:66012825:GC:G	acceptor_gain	0.9900
11:66012825:GCTGG:G	acceptor_gain	0.9900
11:66012948:GGAG:G	donor_gain	0.9900
11:66012285:G:GG	donor_gain	0.9800
11:66012729:ACCT:A	acceptor_gain	0.9800
11:66012827:T:A	acceptor_gain	0.9800
11:66013315:A:AG	acceptor_gain	0.9800
11:66013316:G:GG	acceptor_gain	0.9800
11:66012274:C:T	donor_gain	0.9700
11:66012732:T:A	acceptor_gain	0.9700
11:66012817:T:TA	acceptor_gain	0.9700
11:66012816:A:AG	acceptor_gain	0.9600

AlphaMissense

967 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66013355:G:C	W135C	0.996
11:66013355:G:T	W135C	0.996
11:66013326:T:A	C126S	0.990
11:66013327:G:C	C126S	0.990
11:66012224:C:A	N60K	0.988
11:66012224:C:G	N60K	0.988
11:66012249:T:C	F69L	0.980
11:66012251:C:A	F69L	0.980
11:66012251:C:G	F69L	0.980
11:66012877:T:A	C98S	0.979
11:66012878:G:C	C98S	0.979
11:66012283:A:C	Q80P	0.978
11:66012922:T:A	C113S	0.977
11:66012923:G:C	C113S	0.977
11:66012922:T:C	C113R	0.976
11:66013327:G:A	C126Y	0.976
11:66013332:T:C	F128L	0.976
11:66013334:T:A	F128L	0.976
11:66013334:T:G	F128L	0.976
11:66013353:T:A	W135R	0.976
11:66013353:T:C	W135R	0.976
11:66013326:T:C	C126R	0.974
11:66012872:C:T	T96I	0.972
11:66012208:C:A	A55D	0.968
11:66012851:T:C	L89P	0.968
11:66013333:T:G	F128C	0.967
11:66012835:G:T	G84C	0.966
11:66012844:T:G	Y87D	0.966
11:66013386:T:A	C146S	0.965
11:66013387:G:C	C146S	0.965

dbSNP variants (sampled 300 via entrez): RS1001849317 (11:66013478 C>A), RS1002956166 (11:66011891 A>G), RS1002988565 (11:66012150 G>A), RS1003294198 (11:66010308 C>G,T), RS1003729896 (11:66010554 C>T), RS1004840581 (11:66010446 T>C), RS1004893991 (11:66013793 C>G,T), RS1005706626 (11:66010853 T>C), RS1005722653 (11:66010643 G>T), RS1006888439 (11:66012228 G>GGCA), RS1006899452 (11:66010992 C>T), RS1007549533 (11:66011441 G>A), RS1008318658 (11:66012559 G>A), RS1009240984 (11:66010292 C>T), RS1011551667 (11:66011495 G>T)

Disease associations

OMIM: gene MIM:601891 | disease phenotypes: MIM:618535

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia 15, hypohidrotic/hair type	Strong	Autosomal recessive

Mondo (1): ectodermal dysplasia 15, hypohidrotic/hair type (MONDO:0032804)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000498	Blepharitis
HP:0000613	Photophobia
HP:0000653	Sparse eyelashes
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000966	Hypohidrosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0002209	Sparse scalp hair
HP:0002217	Slow-growing hair
HP:0002231	Sparse body hair
HP:0003577	Congenital onset
HP:0008070	Sparse hair

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST006585_261	Blood protein levels	7.000000e-14
GCST006585_352	Blood protein levels	9.000000e-15
GCST007294_7	Body fat distribution (trunk fat ratio)	8.000000e-12
GCST007294_75	Body fat distribution (trunk fat ratio)	1.000000e-07
GCST007295_158	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_48	Body fat distribution (leg fat ratio)	3.000000e-09
GCST008103_21	Bipolar disorder	2.000000e-08
GCST008839_459	Height	2.000000e-14
GCST010512_19	Serum uric acid levels	2.000000e-11
GCST90020024_397	A body shape index	1.000000e-09
GCST90020025_1882	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_1498	Waist-hip index	4.000000e-10
GCST90020029_334	Waist circumference adjusted for body mass index	3.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004761	uric acid measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression, affects expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Decitabine	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Calcitriol	increases expression	2
Methotrexate	affects response to substance, increases expression	2
Tretinoin	increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
tungsten carbide	affects binding, increases expression	1
urushiol	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression	1
tanshinone	increases expression	1
hydroquinone	increases expression	1
seocalcitol	increases expression	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Arsenic	decreases expression, increases abundance	1
Butyrates	increases expression	1
Cadmium	increases expression	1
Carbamazepine	affects expression	1
Coal Tar	increases expression	1

Clinical trials (associated diseases)

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