HOXC6

Summary

HOXC6 (homeobox C6, HGNC:5128) is a protein-coding gene on chromosome 12q13.13, encoding Homeobox protein Hox-C6 (P09630). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

This gene belongs to the homeobox family, members of which encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene, HOXC6, is one of several HOXC genes located in a cluster on chromosome 12. Three genes, HOXC5, HOXC4 and HOXC6, share a 5’ non-coding exon. Transcripts may include the shared exon spliced to the gene-specific exons, or they may include only the gene-specific exons. Alternatively spliced transcript variants encoding different isoforms have been identified for HOXC6. Transcript variant two includes the shared exon, and transcript variant one includes only gene-specific exons.

Source: NCBI Gene 3223 — RefSeq curated summary.

At a glance

• GWAS associations: 66
• Clinical variants (ClinVar): 2 total
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_004503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5128
Approved symbol	HOXC6
Name	homeobox C6
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000197757
Ensembl biotype	protein_coding
OMIM	142972
Entrez	3223

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000243108, ENST00000394331, ENST00000504315, ENST00000509328

RefSeq mRNA: 2 — MANE Select: NM_004503 NM_004503, NM_153693

CCDS: CCDS41792, CCDS8871

Canonical transcript exons

ENST00000243108 — 2 exons

Exon	Start	End
ENSE00000838340	54028440	54028921
ENSE00000838341	54029655	54030823

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 98.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0415 / max 4.5038, expressed in 17 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125857	7.2060	702
125856	1.6380	554
125860	0.7599	372
125858	0.5836	312
125843	0.3178	106
125861	0.2583	120
125881	0.2437	111
125882	0.1378	57
125862	0.1262	68
125883	0.0415	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	98.77	gold quality
caput epididymis	UBERON:0004358	98.42	gold quality
germinal epithelium of ovary	UBERON:0001304	98.20	gold quality
nipple	UBERON:0002030	97.37	gold quality
saphenous vein	UBERON:0007318	97.22	gold quality
corpus epididymis	UBERON:0004359	97.16	gold quality
skin of hip	UBERON:0001554	97.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.33	gold quality
dorsal root ganglion	UBERON:0000044	95.28	gold quality
mammary duct	UBERON:0001765	95.19	gold quality
synovial joint	UBERON:0002217	95.02	gold quality
epithelium of mammary gland	UBERON:0003244	94.67	gold quality
cauda epididymis	UBERON:0004360	93.79	gold quality
blood vessel layer	UBERON:0004797	93.65	gold quality
diaphragm	UBERON:0001103	92.95	gold quality
tibia	UBERON:0000979	92.86	gold quality
olfactory bulb	UBERON:0002264	92.47	gold quality
vastus lateralis	UBERON:0001379	92.20	gold quality
mammary gland	UBERON:0001911	91.76	gold quality
thoracic mammary gland	UBERON:0005200	91.71	gold quality
quadriceps femoris	UBERON:0001377	91.38	gold quality
upper arm skin	UBERON:0004263	90.76	gold quality
nephron tubule	UBERON:0001231	90.19	gold quality
layer of synovial tissue	UBERON:0007616	90.18	gold quality
upper leg skin	UBERON:0004262	90.04	gold quality
metanephros	UBERON:0000081	89.84	gold quality
kidney epithelium	UBERON:0004819	89.81	gold quality
cortex of kidney	UBERON:0001225	88.53	gold quality
renal glomerulus	UBERON:0000074	88.35	gold quality
left uterine tube	UBERON:0001303	88.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.04

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
ABCB1
BCL2
CD44
FGFR2	Unknown
HOXC5
IGFBP3	Repression
ISL1	Unknown
MME	Repression
NCAM1	Unknown
PDGFRA	Activation
S100B	Activation
TTF1

Upstream regulators (CollecTRI, top): ESR1, ESR2, KDM6A, KMT2A, KMT2B, KMT2C, KMT2D, NCOR1

miRNA regulators (miRDB)

65 targeting HOXC6, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 34)

• proapoptotic repression targets include neutral endopeptidase (NEP) and insulin-like growth factor binding protein-3 (IGFBP-3) (PMID:15637592)
• HOXC6 increases transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwann cells. (PMID:17488478)
• Human cytomegalovirus downregulates while all-trans retinoic acid upregulates expression of hoxc4 and hoxc6 in lymphocytic progenitor cells. (PMID:19236766)
• These studies demonstrated that HOXC6 is an estrogen-responsive gene, and that histone methylases MLL2 and MLL3, in coordination with ERalpha and ERbeta, transcriptionally regulate HOXC6 in an estrogen-dependent manner. (PMID:21683083)
• HOXC6 is an important mechanism of the anti-apoptotic pathway via regulation of Bcl-2 expression. (PMID:22896703)
• HOXC6 expression is an important mechanism of chemotherapeutic drug resistance via its regulation of MDR-1 (PMID:22907429)
• Hoxc6 might contribute to the progression of gastric carcinogenesis and may be a significant predictor of poor survival in patients with gastric cancer after curative operations. (PMID:23581417)
• HOXC6 can be used as a prognostic marker in esophageal squamous cell carcinoma (PMID:24525058)
• Our studies demonstrate that HOXC6, which is a critical player in mammary gland development, is upregulated in multiple cases of breast cancer, and is transcriptionally regulated by E2 and BPA, in vitro and in vivo. (PMID:25725483)
• Data demonstrate significant downregulation of HOXC6 in serous ovarian cancer and low protein level is associated with high-grade tumors. (PMID:26046583)
• HOXC6 has a role in all prostate cancer stages, particularly in prostate cancer cell proliferation. (PMID:26310814)
• HOXC6 thus appears to promote colorectal cancer cell proliferation and tumorigenesis through autophagy inhibition (PMID:27081081)
• HOXC6 mRNA levels were shown to be good predictors for the detection of High-grade Prostate Cancer. (PMID:27108162)
• Increased expression of HOXC6 in gastric cancer cell lines significantly activated extracellular signalregulated kinase signaling and upregulated MMP9. The HOXC6 gene promotes the proliferation of gastric cancer cells while upregulation of MMP9 promotes migration and invasion of gastric cancer cells. (PMID:27573865)
• oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner (PMID:27574949)
• HOXC6 may promote tumor progression by inducing epithelial-mesenchymal transition pathway and predicts poor prognosis of hepatocellular carcinoma. (PMID:29348394)
• our findings indicate that HOXC6 plays an important role in the progress and prognosis of human glioma and promotes glioma U87 cell growth through the WIF-1/Wnt signaling pathway (PMID:30228024)
• HOXC6 up-regulates BCL2 expression and promotes cervical cancer progression. (PMID:30509141)
• These results illuminated that the novel Linc00339/miR-377-3p/HOXC6 axis played a critical role in triple-negative breast cancer (TNBC) progression and might be a promising therapeutic target for TNBC treatment. (PMID:30618083)
• Urinary HOXC6 mRNA levels were quantified and RNA results were then combined with other risk factors in a clinical model optimized to detect International Society of Urological Pathology Grade Group 2 or greater prostate cancer in men with prostate specific antigen less than 10 ng/ml. (PMID:31026217)
• Up-regulated HOXC6, in PCa patients, could not only participate in the progression of PCa but also function as an independent prognostic marker for the cancer (PMID:31271305)
• HoxC6 Functions as an Oncogene and Isoform HoxC6-2 May Play the Primary Role in Gastric Carcinogenesis. (PMID:31900716)
• MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-beta signaling pathway. (PMID:32171324)
• BBOX1 antisense RNA 1 facilitates CC progression by upregulating HOXC6 expression via miR-361-3p and HuR. (PMID:32515533)
• Prospective assessment of two-gene urinary test with multiparametric magnetic resonance imaging of the prostate for men undergoing primary prostate biopsy. (PMID:32681273)
• HomeoboxC6 affects the apoptosis of human vascular endothelial cells and is involved in atherosclerosis. (PMID:32740941)
• HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/beta-catenin axis in right-sided colon cancer. (PMID:33795652)
• TrkB/C-induced HOXC6 activation enhances the ADAM8-mediated metastasis of chemoresistant colon cancer cells. (PMID:33846772)
• HOXC6/8/10/13 predict poor prognosis and associate with immune infiltrations in glioblastoma. (PMID:34763232)
• The Effects of Differentially-Expressed Homeobox Family Genes on the Prognosis and HOXC6 on Immune Microenvironment Orchestration in Colorectal Cancer. (PMID:34950145)
• HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2. (PMID:35008435)
• LINC01857 promotes the proliferation, migration, and invasion of gastric cancer cells via regulating miR-4731-5p/HOXC6. (PMID:35468304)
• High expression of HOXC6 predicts a poor prognosis and induces proliferation and inflammation in multiple myeloma cells. (PMID:37202556)
• [Mechanism of HOXC6 promoting the progression of prostate cancer by activating the SFRP1/Wnt/beta-catenin signaling pathway]. (PMID:39212391)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxc6a	ENSDARG00000070343
danio_rerio	hoxc6b	ENSDARG00000101954
mus_musculus	Hoxc6	ENSMUSG00000001661
rattus_norvegicus	Hoxc6	ENSRNOG00000063956

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), HOXD13 (ENSG00000128714), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-C6 — P09630 (reviewed: P09630)

Alternative names: Homeobox protein CP25, Homeobox protein HHO.C8, Homeobox protein Hox-3C

All UniProt accessions (3): D6RBH4, D6RC34, P09630

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Subcellular location. Nucleus.

Similarity. Belongs to the Antp homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
P09630-1	1	yes
P09630-2	2

RefSeq proteins (2): NP_004494, NP_710160 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001827	Homeobox_Antennapedia_CS	Conserved_site
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050296	Antp_homeobox	Family

Pfam: PF00046

UniProt features (7 total): chain 1, DNA-binding region 1, region of interest 1, short sequence motif 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09630-F1	65.01	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BROWNE_HCMV_INFECTION_6HR_DN, BENPORATH_ES_WITH_H3K27ME3, TGCGCANK_UNKNOWN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, NKX25_02, LFA1_Q6, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, KOINUMA_COLON_CANCER_MSI_UP, GOZGIT_ESR1_TARGETS_DN, RACCACAR_AML_Q6, HNF1_Q6, FOXO4_01, LHX3_01, GGGTGGRR_PAX4_03

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), anterior/posterior pattern specification (GO:0009952), embryonic skeletal system development (GO:0048706), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
regionalization	1
skeletal system development	1
chordate embryonic development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXC6	ISL1	P20663	691
HOXC6	PBX2	P40425	507
HOXC6	TDRD1	Q9BXT4	506
HOXC6	LHX3	Q9UBR4	497
HOXC6	PAX1	P15863	487
HOXC6	HOXB7	P09629	468
HOXC6	ALDH1A2	O94788	431
HOXC6	WNT4	P56705	431
HOXC6	GREB1	Q4ZG55	395
HOXC6	KDR	P35968	383
HOXC6	HOXC12	P31275	381
HOXC6	A0A3B3IT14	A0A3B3IT14	380
HOXC6	FOXP1	Q9H334	380
HOXC6	TBX15	Q96SF7	375
HOXC6	ASH2L	Q9UBL3	373

IntAct

11 interactions, top by confidence:

A	B	Type	Score
HOXC6	rep	psi-mi:“MI:0915”(physical association)	0.370
HOXC6	APC	psi-mi:“MI:0915”(physical association)	0.370
BCAR3	HOXC6	psi-mi:“MI:0915”(physical association)	0.370
CHEK2	HOXC6	psi-mi:“MI:0915”(physical association)	0.370
HOXC6	FGFR2	psi-mi:“MI:0915”(physical association)	0.370
IGF1R	HOXC6	psi-mi:“MI:0915”(physical association)	0.370
PTPRJ	HOXC6	psi-mi:“MI:0915”(physical association)	0.370
HOXC6	TGFB1	psi-mi:“MI:0915”(physical association)	0.370
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RNH1	DUSP11	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): HOXC6 (Two-hybrid), HOXC6 (Two-hybrid), HOXC6 (Two-hybrid), HOXC6 (Two-hybrid), HOXC6 (Two-hybrid), HOXC6 (Two-hybrid), HOXC6 (Two-hybrid), HOXC6 (Affinity Capture-RNA), HOXC6 (Two-hybrid), HOXC6 (Reconstituted Complex), HOXC6 (Affinity Capture-RNA), HOXC6 (Affinity Capture-MS), HOXC6 (Affinity Capture-MS), HOXC6 (Affinity Capture-MS), HOXC6 (Proximity Label-MS)

ESM2 similar proteins: A1YG92, A2T763, A6NJG6, A7Y7W3, G3X9P6, O42504, O57374, P02832, P09025, P09071, P09630, P10629, P14858, P15862, P21711, P24061, P28174, P31273, P42583, P53544, Q1KKS8, Q1KKT1, Q1KKZ6, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q5YLH5, Q6NSW7, Q80Z64, Q8AWZ0, Q8JH55, Q8JJ26, Q8N7R0, Q90470, Q90VZ9, Q91685, Q9DDU1

Diamond homologs: A1YER7, A1YFA5, A1YFD8, A1YFY3, A2D4P8, A2D5I1, A2D5K9, A2D5Y4, A2T6X6, A2T7F3, O13074, O42504, O57374, P02830, P02832, P02833, P04476, P06798, P07548, P09013, P09014, P09016, P09017, P09019, P09020, P09021, P09023, P09024, P09067, P09070, P09071, P09074, P09077, P09079, P09092, P09629, P09630, P10284, P10628, P10629

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
KDM6A	“up-regulates quantity by expression”	HOXC6	“transcriptional regulation”
HOXC6	“up-regulates quantity by expression”	S100B	“transcriptional regulation”
HMGB1	“up-regulates activity”	HOXC6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 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
positive regulation of MAPK cascade	5	36.6×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1977 predictions. Top by Δscore:

Variant	Effect	Δscore
12:54000727:G:GG	donor_gain	1.0000
12:54002419:T:TA	acceptor_gain	1.0000
12:54002420:G:A	acceptor_gain	1.0000
12:54002428:A:AG	acceptor_gain	1.0000
12:54002429:G:GG	acceptor_gain	1.0000
12:54002429:GGC:G	acceptor_gain	1.0000
12:54002429:GGCA:G	acceptor_gain	1.0000
12:54011364:G:GT	donor_gain	1.0000
12:54011375:GGAC:G	donor_gain	1.0000
12:54011376:GAC:G	donor_gain	1.0000
12:54000187:C:CA	acceptor_gain	0.9900
12:54000722:CCCCA:C	donor_gain	0.9900
12:54000723:CCCA:C	donor_gain	0.9900
12:54000724:CCA:C	donor_gain	0.9900
12:54000725:CA:C	donor_gain	0.9900
12:54000725:CAGTA:C	donor_loss	0.9900
12:54000726:AGTA:A	donor_loss	0.9900
12:54000727:GTAA:G	donor_loss	0.9900
12:54000728:T:A	donor_loss	0.9900
12:54002424:CTCCA:C	acceptor_loss	0.9900
12:54002426:CCAG:C	acceptor_loss	0.9900
12:54002428:A:C	acceptor_loss	0.9900
12:54002428:AG:A	acceptor_gain	0.9900
12:54002428:AGGC:A	acceptor_loss	0.9900
12:54002429:G:A	acceptor_loss	0.9900
12:54002429:G:GA	acceptor_gain	0.9900
12:54002429:GG:G	acceptor_gain	0.9900
12:54002429:GGCAA:G	acceptor_gain	0.9900
12:54002710:G:T	donor_gain	0.9900
12:54009717:CACGG:C	donor_loss	0.9900

AlphaMissense

1530 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:54028894:T:A	W125R	1.000
12:54028894:T:C	W125R	1.000
12:54028896:G:C	W125C	1.000
12:54028896:G:T	W125C	1.000
12:54028898:T:C	M126T	1.000
12:54029687:C:A	R145S	1.000
12:54029696:T:C	Y148H	1.000
12:54029696:T:G	Y148D	1.000
12:54029697:A:G	Y148C	1.000
12:54029710:G:C	Q152H	1.000
12:54029710:G:T	Q152H	1.000
12:54029715:T:C	L154P	1.000
12:54029721:T:A	L156Q	1.000
12:54029721:T:C	L156P	1.000
12:54029721:T:G	L156R	1.000
12:54029723:G:A	E157K	1.000
12:54029724:A:T	E157V	1.000
12:54029725:G:C	E157D	1.000
12:54029725:G:T	E157D	1.000
12:54029729:G:A	E159K	1.000
12:54029732:T:A	F160I	1.000
12:54029732:T:C	F160L	1.000
12:54029732:T:G	F160V	1.000
12:54029733:T:C	F160S	1.000
12:54029733:T:G	F160C	1.000
12:54029734:T:A	F160L	1.000
12:54029734:T:G	F160L	1.000
12:54029747:T:C	Y165H	1.000
12:54029747:T:G	Y165D	1.000
12:54029748:A:G	Y165C	1.000

dbSNP variants (sampled 300 via entrez): RS1000059230 (12:54014986 G>A), RS1000137595 (12:54028295 T>G), RS1000191769 (12:54028030 C>G), RS1000269134 (12:54022527 T>C), RS1000413505 (12:54015245 T>C), RS1000563189 (12:54017488 T>C,G), RS1000801908 (12:54017266 T>A), RS1000836494 (12:54020350 T>C), RS1001397497 (12:54025866 A>C), RS1001553715 (12:54022631 C>T), RS1001671760 (12:54017095 T>A,C), RS1001820241 (12:54023014 T>G), RS1001836777 (12:54016594 T>G), RS1002066694 (12:54028215 C>T), RS1002101589 (12:54022097 T>C)

Disease associations

OMIM: gene MIM:142972 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

66 associations (top):

Study	Trait	p-value
GCST001482_26	Lumbar spine bone mineral density	8.000000e-16
GCST002761_10	Hippocampal volume	5.000000e-06
GCST002782_187	Waist-to-hip ratio adjusted for body mass index	3.000000e-14
GCST002782_188	Waist-to-hip ratio adjusted for body mass index	2.000000e-07
GCST002782_189	Waist-to-hip ratio adjusted for body mass index	5.000000e-08
GCST002782_190	Waist-to-hip ratio adjusted for body mass index	3.000000e-13
GCST002782_260	Waist-to-hip ratio adjusted for body mass index	4.000000e-08
GCST002782_261	Waist-to-hip ratio adjusted for body mass index	3.000000e-08
GCST003486_5	Response to fenofibrate (LDL cholesterol levels)	9.000000e-06
GCST004505_47	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-06
GCST004505_48	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	6.000000e-13
GCST004505_49	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	9.000000e-09
GCST004505_50	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-12
GCST004505_51	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	2.000000e-12
GCST004507_40	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	6.000000e-06
GCST004507_44	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-09
GCST004508_7	Waist-to-hip ratio adjusted for BMI in non-smokers	1.000000e-06
GCST004508_8	Waist-to-hip ratio adjusted for BMI in non-smokers	8.000000e-10
GCST004508_9	Waist-to-hip ratio adjusted for BMI in non-smokers	5.000000e-10
GCST004562_112	Waist circumference adjusted for body mass index	1.000000e-08
GCST004562_146	Waist circumference adjusted for body mass index	5.000000e-13
GCST004562_234	Waist circumference adjusted for body mass index	2.000000e-08
GCST004562_42	Waist circumference adjusted for body mass index	2.000000e-14
GCST004562_59	Waist circumference adjusted for body mass index	6.000000e-07
GCST004563_128	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	4.000000e-13
GCST004563_16	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004563_197	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	4.000000e-08
GCST004563_207	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	8.000000e-08
GCST004563_23	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-12
GCST004563_47	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	9.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007804	LDL cholesterol change measurement
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, decreases reaction, increases reaction, decreases expression, increases expression (+1 more)	3
Estradiol	affects binding, decreases reaction, increases reaction, decreases expression, affects reaction (+1 more)	2
Smoke	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
geraniol	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Coumestrol	affects cotreatment, increases expression	1
Cytarabine	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Levonorgestrel	increases expression, affects cotreatment	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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