HOXC13

Summary

HOXC13 (homeobox C13, HGNC:5125) is a protein-coding gene on chromosome 12q13.13, encoding Homeobox protein Hox-C13 (P31276). Transcription factor which plays a role in hair follicle differentiation.

This gene belongs to the homeobox family of genes. The homeobox genes 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 is one of several homeobox HOXC genes located in a cluster on chromosome 12. The product of this gene may play a role in the development of hair, nail, and filiform papilla.

Source: NCBI Gene 3229 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia 9, hair/nail type (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 42
• Clinical variants (ClinVar): 89 total — 5 pathogenic
• Phenotypes (HPO): 20
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_017410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5125
Approved symbol	HOXC13
Name	homeobox C13
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123364
Ensembl biotype	protein_coding
OMIM	142976
Entrez	3229

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000243056

RefSeq mRNA: 1 — MANE Select: NM_017410 NM_017410

CCDS: CCDS8865

Canonical transcript exons

ENST00000243056 — 2 exons

Exon	Start	End
ENSE00000838327	53938831	53939642
ENSE00000838328	53945000	53946544

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 89.77.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1505 / max 823.5444, expressed in 284 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125806	0.9763	251
125809	0.5047	129
125807	0.4007	145
125808	0.1620	82
125805	0.1004	63
125810	0.0064	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hair follicle	UBERON:0002073	89.77	gold quality
type B pancreatic cell	CL:0000169	89.04	silver quality
olfactory bulb	UBERON:0002264	89.02	gold quality
vena cava	UBERON:0004087	86.65	gold quality
tongue squamous epithelium	UBERON:0006919	86.54	gold quality
cervix squamous epithelium	UBERON:0006922	86.02	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.17	gold quality
diaphragm	UBERON:0001103	83.53	silver quality
cerebellar vermis	UBERON:0004720	83.41	silver quality
cardia of stomach	UBERON:0001162	83.19	silver quality
thymus	UBERON:0002370	79.73	gold quality
vastus lateralis	UBERON:0001379	79.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.98	gold quality
upper arm skin	UBERON:0004263	78.69	silver quality
body of tongue	UBERON:0011876	78.45	gold quality
tongue	UBERON:0001723	77.93	gold quality
superior surface of tongue	UBERON:0007371	77.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	76.96	gold quality
male germ cell	CL:0000015	76.60	gold quality
ventral tegmental area	UBERON:0002691	76.54	gold quality
synovial joint	UBERON:0002217	76.50	gold quality
pharyngeal mucosa	UBERON:0000355	76.46	gold quality
trachea	UBERON:0003126	76.41	gold quality
pericardium	UBERON:0002407	76.19	gold quality
lateral globus pallidus	UBERON:0002476	76.16	gold quality
substantia nigra pars reticulata	UBERON:0001966	76.15	gold quality
superior vestibular nucleus	UBERON:0007227	76.15	gold quality
pons	UBERON:0000988	75.95	gold quality
substantia nigra pars compacta	UBERON:0001965	75.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	38.16
E-ANND-3	no	0.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CRISP3
DSG4	Repression
FOXN1	Activation
HBB	Repression
LAMB2	Activation
SPI1	Repression
ZNF521	Activation

JASPAR motifs

Motif	Name	Family
MA0907.1	HOXC13	HOX
MA0907.2	HOXC13	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): ESR1, ESR2, EZH2, KDM6A, KMT2A, KMT2B

miRNA regulators (miRDB)

76 targeting HOXC13, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4534	99.99	66.58	1907
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-6793-5P	99.97	65.95	758
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4779	99.86	66.50	1583

Literature-anchored findings (GeneRIF, showing 26)

• Krtap16 is a hair keratin-associated protein gene complex regulated by Hoxc13 (PMID:15385554)
• HOXC13 was highly expressed in ameloblastoma. Heterogeneous expression could improve the epithelial proliferation, and its loss may lead to the cornification and degeneration of epithelial cells. (PMID:17331444)
• Results show that HOXC13 is a member of human replicative complexes. (PMID:19182517)
• To our knowledge, this is the first case of t(11;12)(p15;q13) in de novo AML-M4 in association with FLT3 ITD mutation. Coexistence of NUP98-HOXC13 fusion and FLT3 ITD mutation is likely relevant in the process of leukemogenesis (PMID:19665070)
• knockdown of BMI-1 expression can induce cell-cycle arrest and up-regulate p16INK4a, HOXA9 and HOXC13 in HeLa cells (PMID:20661663)
• results show the strong and progressive HOX C13 overexpression in metastatic melanoma tissues and cytological samples compared to nevi and primary melanoma tissues and cells. (PMID:22583695)
• loss-of-function mutations in HOXC13 cause autosomal-recessive PHNED and further highlight the importance of HOXC13 in hair and nail development. (PMID:23063621)
• Identification of a homozygous mutation in the HOXC13 gene in a Syrian family with autosomal-recessive pure hair and nail ectodermal dysplasia. (PMID:23315978)
• Results show that duplication and nonsense mutation lead to loss of function in this gene and the role it plays in hair and nail development (PMID:23461661)
• In conclusion, our data show a deregulation of the HOXC13 marker in welldifferentiated and dedifferentiated LPSs, possibly related to 12q13-15 chromosomal amplification. (PMID:24085196)
• YAP regulates the expression of HOXA1 and HOXC13 in human keratinocytes. (PMID:25691658)
• The microdeletions share a minimal non-coding region overlap upstream of HOXC13, with variable phenotypes depending upon HOXC13, HOXC12 or thIdentification of 5’ HOXC microdeletions highlights the importance of transcriptional regulators in the aetiology of severe lower limb malformations and will improve their diagnosis and managemente HOTAIR lncRNA inclusion. (PMID:26729820)
• Mutations in Hoxc13 is associated with ectodermal dysplasia-9. (PMID:28011715)
• A novel missense mutation (c.929A > C) in HOXC13 gene associated with pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family. (PMID:28403827)
• we report a novel nonsense variant (c.265C>T, p.Gln89*) in the HOXC13 gene, which resulted in a premature termination codon and is predicted either to produce a truncated protein without an essential DNA binding homeodomain or more likely to undergo nonsense-mediated RNA decay- ultimately producing the PHNED (pure hair and nail ectodermal dysplasia) phenotype. (PMID:28543635)
• Study showed that HOXC13 expression was significantly elevated in esophageal squamous cell carcinoma (ESCC), and correlated with worse clinical characteristics and poorer prognosis. HOXC13 promoted proliferation and inhibited apoptosis through repressing transcription of CASP3. (PMID:29168599)
• The results have identified a homozygous 28 base-pair insertion mutation in exon 2 of the HOXC13 gene in both sisters in an Iranian family. This mutation was also present in both parents in the heterozygous state. (PMID:29278420)
• that HOXC13-AS exerted oncogenic function in nasopharyngeal carcinoma via regulating miR-383-3p/HMGA2 axis (PMID:30536950)
• The homeobox transcription factor HOXC13 upregulates human papillomavirus E1 gene expression and contributes to viral genome maintenance. (PMID:31642514)
• HOXC13-AS accelerates cell proliferation and migration in oral squamous cell carcinoma via miR-378g/HOXC13 axis. (PMID:32763778)
• HOXC-AS2 mediates the proliferation, apoptosis, and migration of non-small cell lung cancer by combining with HOXC13 gene. (PMID:33427025)
• HOXC13 promotes cervical cancer proliferation, invasion and Warburg effect through beta-catenin/c-Myc signaling pathway. (PMID:34309767)
• HOXC6/8/10/13 predict poor prognosis and associate with immune infiltrations in glioblastoma. (PMID:34763232)
• LncRNA HOXC-AS5 Affects the Proliferation, Invasion and Cell Cycle of Ameloblastoma Cells by Acting on the Target Gene HOXC13. (PMID:36029503)
• Variants Identified in the HOXC13 and HOXD13 Genes Suggest Association with Cervical Cancer in a Cohort of Mexican Women. (PMID:36833285)
• Silencing HOXC13 exerts anti-prostate cancer effects by inducing DNA damage and activating cGAS/STING/IRF3 pathway. (PMID:38057852)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxc13a	ENSDARG00000070353
danio_rerio	hoxc13b	ENSDARG00000113877
mus_musculus	Hoxc13	ENSMUSG00000001655
rattus_norvegicus	Hoxc13	ENSRNOG00000028679

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), 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), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-C13 — P31276 (reviewed: P31276)

Alternative names: Homeobox protein Hox-3G

All UniProt accessions (1): P31276

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor which plays a role in hair follicle differentiation. Regulates FOXQ1 expression and that of other hair-specific genes.

Subcellular location. Nucleus.

Disease relevance. Ectodermal dysplasia 9, hair/nail type (ECTD9) [MIM:614931] A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD9 is characterized by hypotrichosis and nail dystrophy without non-ectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia). The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_059106* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR022067	HoxA13_N	Domain
IPR051003	AP_axis_regulatory_Homeobox	Family

Pfam: PF00046, PF12284

UniProt features (7 total): sequence variant 2, chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31276-F1	58.40	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 167 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOZGIT_ESR1_TARGETS_DN, TGACCTY_ERR1_Q2, USF_C, GOBP_TONGUE_DEVELOPMENT, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_APPENDAGE_DEVELOPMENT, SHIN_B_CELL_LYMPHOMA_CLUSTER_2, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, CTTTGTA_MIR524, GOBP_SKIN_DEVELOPMENT

GO Biological Process (9): hair follicle development (GO:0001942), regulation of transcription by RNA polymerase II (GO:0006357), anatomical structure morphogenesis (GO:0009653), anterior/posterior pattern specification (GO:0009952), nail development (GO:0035878), tongue morphogenesis (GO:0043587), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): transcription cis-regulatory region binding (GO:0000976), 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 transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
binding	2
hair cycle process	1
skin epidermis development	1
developmental process	1
regionalization	1
limb development	1
tongue development	1
sensory organ morphogenesis	1
positive regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transcription factor binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXC13	FOXN1	O15353	727
HOXC13	NUP98	P52948	691
HOXC13	FOXQ1	Q9C009	677
HOXC13	DDX10	Q13206	635
HOXC13	RAP1GDS1	P52306	630
HOXC13	LEF1	Q9UJU2	597
HOXC13	KRT35	Q92764	593
HOXC13	HOXC4	P09017	588
HOXC13	PSIP1	O75475	584
HOXC13	PRRX1	P54821	581
HOXC13	NSD1	Q96L73	559
HOXC13	DSG4	Q86SJ6	550
HOXC13	HOXC5	Q00444	546
HOXC13	NSD3	Q9BZ95	542
HOXC13	PHF23	Q9BUL5	526

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FOXP1	FOXP2	psi-mi:“MI:0914”(association)	0.910
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
HOXC13	ELF1	psi-mi:“MI:0915”(physical association)	0.520
ELF1	HOXC13	psi-mi:“MI:0915”(physical association)	0.520
HOXC13	NFATC1	psi-mi:“MI:0915”(physical association)	0.500
HOXC13	NR2E3	psi-mi:“MI:0915”(physical association)	0.370
HNRNPAB	HOXC13	psi-mi:“MI:0915”(physical association)	0.370
HOXC9	HOXC13	psi-mi:“MI:0915”(physical association)	0.370
APEX1	HOXC13	psi-mi:“MI:0915”(physical association)	0.370
HOXC13	RHOXF2	psi-mi:“MI:0915”(physical association)	0.370
FOXC1	NFIX	psi-mi:“MI:0914”(association)	0.350
FOXC2	ZNF536	psi-mi:“MI:0914”(association)	0.350
FOXD3	HOXC13	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXG1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXI2	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
FOXN1	FOXN1	psi-mi:“MI:0914”(association)	0.350
FOXO1	HOXC13	psi-mi:“MI:0914”(association)	0.350
FOXR1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
FOXS1	DDX39A	psi-mi:“MI:0914”(association)	0.350
NFATC1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXD3	MYL12B	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Affinity Capture-MS), HOXC13 (Proximity Label-MS), HOXC13 (Negative Genetic), HOXC13 (Proximity Label-MS), HOXC13 (Protein-peptide)

ESM2 similar proteins: A0PJS5, A1YG01, A2D4R4, A2D649, A2T6H5, A2T6Z0, A3KNJ3, A7Y7W3, A8K830, F6W2R2, F8VPY8, O15353, O42506, O43186, O54751, P14653, P17919, P28322, P31276, P32243, P40646, P43268, P57082, P70056, P80206, P83758, Q00288, Q06710, Q08820, Q16633, Q1KL10, Q28GC4, Q28IU6, Q2KJA4, Q4G112, Q503Z8, Q64693, Q66IK1, Q66IT9, Q7T1C0

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, G5EFY5, O14627, O42502, O42506, O43248, P02835, P09013, P09067, P09079, P09087, P09631, P09633, P10038, P10179, P17482, P17919, P20615, P23812, P24061, P24341, P24342, P24343, P24344, P28358, P28359, P31257, P31260, P31263, P31268, P31269, P31271, P31272, P31274, P31275

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
HOXC13	“up-regulates quantity by expression”	FOXN1	“transcriptional regulation”
HOXC13	“down-regulates quantity by repression”	DSG4	“transcriptional regulation”
KDM6A	“up-regulates quantity by expression”	HOXC13	“transcriptional regulation”
HOXC13	“up-regulates quantity by expression”	LAMB2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
anatomical structure morphogenesis	6	25.3×	9e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — BRCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	69
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1701201	NM_017410.3(HOXC13):c.861_862insACTTGCGGCTAGCAAGTTCATCACCAAA (p.Glu288delinsThrCysGlyTer)	Pathogenic
2723989	NM_017410.3(HOXC13):c.131dup (p.Gly45fs)	Pathogenic
39781	NM_017410.3(HOXC13):c.390C>A (p.Tyr130Ter)	Pathogenic
39782	NM_017410.2(HOXC13):c.-24497_736+2389del	Pathogenic
50641	NM_017410.3(HOXC13):c.355del (p.Leu119fs)	Pathogenic

SpliceAI

170 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53944998:A:AG	acceptor_gain	1.0000
12:53944999:G:GC	acceptor_gain	1.0000
12:53944999:GAC:G	acceptor_gain	1.0000
12:53944999:GACGT:G	acceptor_gain	1.0000
12:53939626:G:GT	donor_gain	0.9900
12:53939639:CCAGG:C	donor_loss	0.9900
12:53939640:CAGG:C	donor_loss	0.9900
12:53939641:AGGT:A	donor_loss	0.9900
12:53939642:GGT:G	donor_loss	0.9900
12:53939643:GTAAG:G	donor_loss	0.9900
12:53939644:T:G	donor_loss	0.9900
12:53944996:GCAG:G	acceptor_loss	0.9900
12:53944997:CAGAC:C	acceptor_loss	0.9900
12:53944998:A:T	acceptor_loss	0.9900
12:53944998:AGAC:A	acceptor_gain	0.9900
12:53944999:GACG:G	acceptor_gain	0.9900
12:53944999:GA:G	acceptor_gain	0.9700
12:53944995:C:CA	acceptor_gain	0.9600
12:53944997:CAGA:C	acceptor_gain	0.9600
12:53944989:T:G	acceptor_gain	0.9500
12:53944988:A:AG	acceptor_gain	0.9400
12:53944996:GCAGA:G	acceptor_gain	0.9400
12:53944995:CGCA:C	acceptor_gain	0.9300
12:53944998:AGACG:A	acceptor_gain	0.9200
12:53939643:G:GG	donor_gain	0.8900
12:53940690:G:GT	donor_gain	0.8800
12:53944994:CCGCA:C	acceptor_gain	0.8700
12:53944999:G:T	acceptor_gain	0.8400
12:53939626:G:T	donor_gain	0.8300
12:53939648:G:GT	donor_gain	0.8200

AlphaMissense

2126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53945049:G:C	K262N	1.000
12:53945049:G:T	K262N	1.000
12:53945053:C:A	R264S	1.000
12:53945053:C:T	R264C	1.000
12:53945060:C:A	P266H	1.000
12:53945062:T:A	Y267N	1.000
12:53945062:T:C	Y267H	1.000
12:53945062:T:G	Y267D	1.000
12:53945063:A:G	Y267C	1.000
12:53945076:G:C	Q271H	1.000
12:53945076:G:T	Q271H	1.000
12:53945078:T:C	L272P	1.000
12:53945087:T:A	L275Q	1.000
12:53945087:T:C	L275P	1.000
12:53945087:T:G	L275R	1.000
12:53945090:A:T	E276V	1.000
12:53945091:G:C	E276D	1.000
12:53945091:G:T	E276D	1.000
12:53945095:G:A	E278K	1.000
12:53945098:T:C	Y279H	1.000
12:53945098:T:G	Y279D	1.000
12:53945099:A:C	Y279S	1.000
12:53945099:A:G	Y279C	1.000
12:53945113:T:A	F284I	1.000
12:53945113:T:C	F284L	1.000
12:53945113:T:G	F284V	1.000
12:53945114:T:C	F284S	1.000
12:53945114:T:G	F284C	1.000
12:53945115:C:A	F284L	1.000
12:53945115:C:G	F284L	1.000

dbSNP variants (sampled 300 via entrez): RS1000039708 (12:53939835 T>C), RS1000091934 (12:53940069 C>A), RS1000751974 (12:53939654 AC>A), RS1001005412 (12:53944870 T>C), RS1001046001 (12:53938485 C>A,T), RS1001096715 (12:53938671 C>G), RS1001660568 (12:53940830 A>G), RS1001971418 (12:53945550 G>A,C,T), RS1002082706 (12:53946031 T>C), RS1002264858 (12:53938926 T>C), RS1002864789 (12:53937794 A>G), RS1003350909 (12:53942636 C>T), RS1003389997 (12:53938094 TGA>T), RS1004170813 (12:53942577 C>T), RS1004666823 (12:53937186 C>G)

Disease associations

OMIM: gene MIM:142976 | disease phenotypes: MIM:614931

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia 9, hair/nail type	Definitive	Autosomal recessive
pure hair and nail ectodermal dysplasia	Supportive	Autosomal dominant

Mondo (2): ectodermal dysplasia 9, hair/nail type (MONDO:0013976), pure hair and nail ectodermal dysplasia (MONDO:0019071)

Orphanet (1): Pure hair and nail ectodermal dysplasia (Orphanet:69084)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000164	Abnormality of the dentition
HP:0000478	Abnormality of the eye
HP:0000561	Absent eyelashes
HP:0000707	Abnormality of the nervous system
HP:0000924	Abnormality of the skeletal system
HP:0000968	Ectodermal dysplasia
HP:0000971	Abnormal sweat gland morphology
HP:0001598	Concave nail
HP:0001792	Small nail
HP:0002223	Absent eyebrow
HP:0002298	Absent hair
HP:0003577	Congenital onset
HP:0008070	Sparse hair
HP:0008404	Nail dystrophy
HP:0012741	Unilateral cryptorchidism
HP:0032226	Abnormal sebaceous gland morphology
HP:0040039	Onycholysis of fingernails
HP:0500262	Atrichia

GWAS associations

42 associations (top):

Study	Trait	p-value
GCST000681_2	Biliary atresia	9.000000e-06
GCST000829_7	Waist-hip ratio	6.000000e-17
GCST002005_1	Adverse response to chemotherapy (neutropenia/leucopenia) (all antimetabolite drugs)	4.000000e-06
GCST002337_95	Amyotrophic lateral sclerosis (sporadic)	6.000000e-06
GCST002671_11	Toenail selenium levels	8.000000e-07
GCST002782_230	Waist-to-hip ratio adjusted for body mass index	1.000000e-14
GCST002782_231	Waist-to-hip ratio adjusted for body mass index	7.000000e-13
GCST002782_232	Waist-to-hip ratio adjusted for body mass index	8.000000e-16
GCST002782_233	Waist-to-hip ratio adjusted for body mass index	1.000000e-13
GCST004064_43	Waist-hip ratio	3.000000e-11
GCST004064_8	Waist-hip ratio	2.000000e-13
GCST004505_45	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-10
GCST004505_46	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	2.000000e-11
GCST004507_16	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	5.000000e-07
GCST004507_33	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	5.000000e-07
GCST004508_5	Waist-to-hip ratio adjusted for BMI in non-smokers	3.000000e-07
GCST004508_6	Waist-to-hip ratio adjusted for BMI in non-smokers	5.000000e-07
GCST004567_103	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	5.000000e-12
GCST004567_11	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	5.000000e-12
GCST004567_117	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-13
GCST004567_30	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-13
GCST004576_88	Waist-to-hip ratio adjusted for body mass index	5.000000e-13
GCST004576_89	Waist-to-hip ratio adjusted for body mass index	1.000000e-13
GCST004576_90	Waist-to-hip ratio adjusted for body mass index	4.000000e-13
GCST004576_91	Waist-to-hip ratio adjusted for body mass index	3.000000e-13
GCST004578_139	Waist-to-hip ratio adjusted for BMI in active individuals	3.000000e-12
GCST004578_43	Waist-to-hip ratio adjusted for BMI in active individuals	6.000000e-14
GCST004578_58	Waist-to-hip ratio adjusted for BMI in active individuals	3.000000e-12
GCST004578_81	Waist-to-hip ratio adjusted for BMI in active individuals	6.000000e-14
GCST005191_8	Hair shape	1.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0003924	hair color
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance	2
Cisplatin	increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
arsenite	increases methylation	1
afimoxifene	decreases expression, decreases reaction	1
nickel sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Camptothecin	increases expression	1
Coumestrol	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Endosulfan	increases expression	1
Estrogens	decreases expression, decreases reaction	1
Ozone	increases expression, increases oxidation	1
Tunicamycin	decreases expression	1
Vanadates	increases expression	1
Aflatoxin B1	decreases methylation	1
Hydroxyl Radical	increases expression, increases oxidation	1
Cadmium Chloride	decreases expression	1
Thapsigargin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2Z3	SEES3-1V human HOXC13, clone1	Embryonic stem cell	Male
CVCL_A2Z4	SEES3-1V human HOXC13, clone2	Embryonic stem cell	Male
CVCL_A2Z5	SEES3-1V human HOXC13, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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