COL27A1

Summary

COL27A1 (collagen type XXVII alpha 1 chain, HGNC:22986) is a protein-coding gene on chromosome 9q32, encoding Collagen alpha-1(XXVII) chain (Q8IZC6). Plays a role during the calcification of cartilage and the transition of cartilage to bone.

This gene encodes a member of the fibrillar collagen family, and plays a role during the calcification of cartilage and the transition of cartilage to bone. The encoded protein product is a preproprotein. It includes an N-terminal signal peptide, which is followed by an N-terminal propetide, mature peptide and a C-terminal propeptide. The N-terminal propeptide contains thrombospondin N-terminal-like and laminin G-like domains. The mature peptide is a major triple-helical region. The C-terminal propeptide, also known as COLFI domain, plays crucial roles in tissue growth and repair. Mutations in this gene cause Steel syndrome. Alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been determined.

Source: NCBI Gene 85301 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Steel syndrome (Definitive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 2,512 total — 79 pathogenic, 77 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_032888

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22986
Approved symbol	COL27A1
Name	collagen type XXVII alpha 1 chain
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1870, MGC11337, FLJ11895
Ensembl gene	ENSG00000196739
Ensembl biotype	protein_coding
OMIM	608461
Entrez	85301

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding_CDS_not_defined, 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000356083, ENST00000451716, ENST00000468565, ENST00000477421, ENST00000485397, ENST00000490831, ENST00000494090, ENST00000494780

RefSeq mRNA: 1 — MANE Select: NM_032888 NM_032888

CCDS: CCDS6802

Canonical transcript exons

ENST00000356083 — 61 exons

Exon	Start	End
ENSE00001323611	114162715	114162785
ENSE00001462493	114310549	114312511
ENSE00001462512	114155537	114156012
ENSE00001608196	114222223	114222267
ENSE00001623452	114205759	114205812
ENSE00001632380	114231079	114231132
ENSE00001667511	114209675	114209728
ENSE00001692097	114252593	114252646
ENSE00001699498	114206252	114206296
ENSE00001702790	114205102	114205146
ENSE00001702822	114219791	114219844
ENSE00001730673	114195959	114196012
ENSE00001739649	114167689	114169463
ENSE00001741527	114231822	114231866
ENSE00001766211	114210982	114211026
ENSE00001766445	114194404	114194457
ENSE00001792281	114178291	114178344
ENSE00001805015	114183022	114183075
ENSE00003469961	114288914	114288967
ENSE00003470199	114258541	114258594
ENSE00003470695	114283709	114283762
ENSE00003473069	114302082	114302108
ENSE00003475888	114252879	114252932
ENSE00003475900	114301445	114301462
ENSE00003480049	114301682	114301717
ENSE00003486419	114264355	114264408
ENSE00003486916	114265066	114265110
ENSE00003489819	114288702	114288755
ENSE00003493823	114300070	114300123
ENSE00003502479	114290058	114290111
ENSE00003503924	114265422	114265475
ENSE00003512023	114282277	114282330
ENSE00003516224	114245866	114245910
ENSE00003521453	114240434	114240487
ENSE00003530254	114243507	114243560
ENSE00003531080	114237662	114237715
ENSE00003544017	114289242	114289295
ENSE00003546346	114304608	114304673
ENSE00003557252	114267504	114267557
ENSE00003558472	114240220	114240273
ENSE00003600783	114250615	114250668
ENSE00003608492	114269241	114269294
ENSE00003614424	114306520	114306688
ENSE00003615162	114284724	114284777
ENSE00003615740	114301072	114301125
ENSE00003638076	114264924	114264968
ENSE00003638638	114236981	114237034
ENSE00003642474	114266565	114266618
ENSE00003642543	114275661	114275768
ENSE00003643130	114307669	114307778
ENSE00003646724	114242187	114242231
ENSE00003654209	114235599	114235652
ENSE00003657626	114282457	114282564
ENSE00003659789	114301284	114301319
ENSE00003662351	114288455	114288511
ENSE00003662895	114290810	114290917
ENSE00003674033	114290224	114290331
ENSE00003677287	114270728	114270781
ENSE00003678807	114309260	114309478
ENSE00003686883	114300625	114300687
ENSE00003687112	114292103	114292210

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6167 / max 513.9478, expressed in 1360 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98142	6.3773	1299
98141	0.5707	282
98147	0.5595	246
98144	0.2982	135
98146	0.2826	130
205600	0.2094	64
98143	0.1864	78
98145	0.1327	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.82	gold quality
cerebellar vermis	UBERON:0004720	98.79	gold quality
pancreatic ductal cell	CL:0002079	98.37	gold quality
endocervix	UBERON:0000458	97.63	gold quality
pylorus	UBERON:0001166	97.41	gold quality
cartilage tissue	UBERON:0002418	97.28	gold quality
cerebellar hemisphere	UBERON:0002245	96.85	gold quality
cerebellum	UBERON:0002037	96.84	gold quality
cerebellar cortex	UBERON:0002129	96.81	gold quality
renal medulla	UBERON:0000362	96.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.57	gold quality
upper arm skin	UBERON:0004263	96.38	gold quality
sural nerve	UBERON:0015488	96.15	gold quality
uterine cervix	UBERON:0000002	95.89	gold quality
buccal mucosa cell	CL:0002336	95.66	gold quality
ectocervix	UBERON:0012249	95.47	gold quality
kidney epithelium	UBERON:0004819	94.97	gold quality
cardia of stomach	UBERON:0001162	94.92	gold quality
metanephros cortex	UBERON:0010533	94.74	gold quality
corpus epididymis	UBERON:0004359	94.53	gold quality
pericardium	UBERON:0002407	94.50	gold quality
dorsal root ganglion	UBERON:0000044	94.48	gold quality
cauda epididymis	UBERON:0004360	94.43	gold quality
trigeminal ganglion	UBERON:0001675	94.12	gold quality
right lobe of liver	UBERON:0001114	93.68	gold quality
seminal vesicle	UBERON:0000998	93.44	gold quality
left ventricle myocardium	UBERON:0006566	93.30	gold quality
epithelial cell of pancreas	CL:0000083	93.06	gold quality
body of uterus	UBERON:0009853	92.63	gold quality
vagina	UBERON:0000996	92.38	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	320.01
E-GEOD-81608	yes	16.29
E-ANND-3	yes	8.39
E-MTAB-8410	yes	4.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, MAF

miRNA regulators (miRDB)

127 targeting COL27A1, 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-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-8068	99.98	73.85	2376

Literature-anchored findings (GeneRIF, showing 15)

• molecular cloning (PMID:12714037)
• type XXVII collagen has unusual molecular features such as no minor helical domain, a major helical domain that is short and interrupted, and a short chain selection sequence within the NC1 domain (PMID:12766169)
• SOX9 may play an important role in the transcriptional activation of the newest collagen gene, COL27A1. (PMID:15922909)
• The results of this study found in rs7868992 on chromosome 9q32 within COL27A1 is releate to Tourette’s syndrome. (PMID:22889924)
• This study further implicates the genomic region containing the TNC and COL27A1 genes in influencing risk of Achilles tendinopathy, and maps the potential risk allele to a genetic interval flanked by rs946053 and rs2104772. (PMID:23192621)
• Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population (PMID:24986830)
• Genetic analysis between COL27A1 and Tourette syndrome was performed. (PMID:26235311)
• Our report further validates the role of COL27A1 mutations in causation of Steel syndrome. (PMID:28276056)
• we conclude that the novel splice-site variant identified in COL27A1 is the most likely cause for Steel syndrome in this family and that the hearing loss is part of this syndrome’s phenotype (PMID:28322503)
• analysis of genetic variants of COL27A1 and tenascin C in achilles tendinopathy and anterior cruciate ligament ruptures (PMID:30359423)
• two loci in or near GDF5 and COL27A1 that are associated with knee pain, were identified. (PMID:31482140)
• Three new patients with Steel syndrome and a Puerto Rican specific COL27A1 mutation. (PMID:31903681)
• First reported case of Steel syndrome in the European population: A novel homozygous mutation in COL27A1 and review of the literature. (PMID:32360765)
• Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide. (PMID:32376988)
• Brothers with novel compound heterozygous mutations in COL27A1 causing dental and genital abnormalities. (PMID:33359165)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Col27a1	ENSMUSG00000045672
rattus_norvegicus	Col27a1	ENSRNOG00000007657

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COLQ (ENSG00000206561), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Collagen alpha-1(XXVII) chain — Q8IZC6 (reviewed: Q8IZC6)

All UniProt accessions (3): Q8IZC6, H0YD40, Q5T1U7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role during the calcification of cartilage and the transition of cartilage to bone.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Disease relevance. Steel syndrome (STLS) [MIM:615155] A syndrome characterized by dislocated hips and radial heads, fusion of carpal bones, short stature, scoliosis, and cervical spine anomalies. Facial features include prominent forehead, long oval-shaped face, hypertelorism and broad nasal bridge. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function.

Similarity. Belongs to the fibrillar collagen family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IZC6-1	1	yes
Q8IZC6-2	2
Q8IZC6-3	3

RefSeq proteins (1): NP_116277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000885	Fib_collagen_C	Domain
IPR008160	Collagen	Repeat
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR048287	TSPN-like_N	Domain
IPR050938	Collagen_Structural_Proteins	Family

Pfam: PF01391, PF01410

UniProt features (75 total): compositionally biased region 22, domain 18, sequence variant 13, disulfide bond 5, region of interest 4, binding site 4, splice variant 3, propeptide 2, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZC6-F1	49.13	0.09

Functional residue map

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

Ligand- & substrate-binding residues (4): 1708; 1710; 1713; 1716

Disulfide bonds (5): 1690–1722, 1696, 1713, 1731–1858, 1767–1811

Glycosylation sites (2): 271, 1769

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-8948216	Collagen chain trimerization
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells

MSigDB gene sets: 277 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, AP1_01, BENPORATH_ES_WITH_H3K27ME3, PAX4_01, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOCC_COLLAGEN_TRIMER, PEREZ_TP63_TARGETS, GOBP_GROWTH, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_CHONDROCYTE_DEVELOPMENT, GOBP_BONE_GROWTH, BILD_HRAS_ONCOGENIC_SIGNATURE

GO Biological Process (3): skeletal system development (GO:0001501), growth plate cartilage chondrocyte development (GO:0003431), extracellular matrix organization (GO:0030198)

GO Molecular Function (3): extracellular matrix structural constituent conferring tensile strength (GO:0030020), metal ion binding (GO:0046872), extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (6): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), collagen type XXVII trimer (GO:1990325), collagen trimer (GO:0005581), fibrillar collagen trimer (GO:0005583)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Collagen formation	2
MET promotes cell motility	1
Collagen biosynthesis and modifying enzymes	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
growth plate cartilage chondrocyte differentiation	1
chondrocyte development involved in endochondral bone morphogenesis	1
extracellular structure organization	1
external encapsulating structure organization	1
extracellular matrix structural constituent	1
cation binding	1
structural molecule activity	1
extracellular matrix	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
fibrillar collagen trimer	1
protein-containing complex	1
collagen trimer	1
fibrillar collagen complex	1
extracellular protein-containing complex	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL27A1	LAMC1	P11047	766
COL27A1	COL5A1	P20908	580
COL27A1	COL4A2	P08572	560
COL27A1	COL16A1	Q07092	531
COL27A1	CNIH3	Q8TBE1	525
COL27A1	CNIH1	O95406	523
COL27A1	COL12A1	Q99715	496
COL27A1	COL6A3	P12111	483
COL27A1	COL11A1	P12107	472
COL27A1	COL5A3	P25940	465
COL27A1	COL4A3	Q01955	465
COL27A1	COL4A1	P02462	461
COL27A1	COL2A1	P02458	450
COL27A1	COL13A1	Q5TAT6	446
COL27A1	COL10A1	Q03692	445

IntAct

8 interactions, top by confidence:

A	B	Type	Score
COL27A1	E7	psi-mi:“MI:0915”(physical association)	0.490
COL27A1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
COL27A1	E2	psi-mi:“MI:0915”(physical association)	0.370
COL27A1	E7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (14): COL27A1 (Two-hybrid), COL27A1 (Affinity Capture-MS), COL27A1 (Affinity Capture-MS), COL27A1 (Affinity Capture-MS), EEF1G (Cross-Linking-MS (XL-MS)), COL27A1 (Cross-Linking-MS (XL-MS)), COL27A1 (Two-hybrid), COL27A1 (PCA), COL27A1 (PCA), EEF1G (Cross-Linking-MS (XL-MS)), COL27A1 (Co-fractionation), COL27A1 (Co-fractionation), COL27A1 (Co-fractionation), COL27A1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WR59, C0HLN2, C7DZK3, O35167, O35348, O76368, O88207, P08122, P08572, P12106, P12107, P12108, P13942, P20849, P20850, P20908, P20909, P25067, P25940, P53420, P83371, P98085, Q01955, Q03637, Q05722, Q07092, Q07643, Q0VF58, Q14031, Q14055, Q14993, Q17RW2, Q28083, Q30D77, Q32S24, Q4ZJM7

Diamond homologs: A0MSJ1, C7DZK3, O42350, O88207, P02452, P02457, P02458, P02459, P02460, P02461, P02466, P05997, P08121, P12105, P12107, P13941, P13942, P20908, P20909, Q17RW2, Q30D77, Q32S24, Q3U962, Q5QNQ9, Q60467, Q61245, Q64739, Q6P4Z2, Q80ZF0, Q8IZC6, Q91717, Q9JI03, Q9YIB4, P25940, Q28668, B8V7R6, C0HM84, C0HM85, C0HM86, C0HM87

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2512 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	79
Likely pathogenic	77
Uncertain significance	527
Likely benign	1606
Benign	115

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027381	NM_032888.4(COL27A1):c.4519C>T (p.Arg1507Ter)	Pathogenic
1069452	NM_032888.4(COL27A1):c.697_707del (p.Arg233fs)	Pathogenic
1071799	NM_032888.4(COL27A1):c.2797C>T (p.Arg933Ter)	Pathogenic
1072509	NM_032888.4(COL27A1):c.3365dup (p.Gly1123fs)	Pathogenic
1073584	NM_032888.4(COL27A1):c.3518_3519insAGGG (p.Thr1175fs)	Pathogenic
1073916	NM_032888.4(COL27A1):c.3248del (p.Lys1083fs)	Pathogenic
1322126	NM_032888.4(COL27A1):c.3294+1G>C	Pathogenic
1334897	NM_032888.4(COL27A1):c.4060C>T (p.Arg1354Ter)	Pathogenic
1372660	NM_032888.4(COL27A1):c.2576_2577insT (p.Val860fs)	Pathogenic
1412773	NM_032888.4(COL27A1):c.924_927dup (p.Gln310fs)	Pathogenic
1413408	NM_032888.4(COL27A1):c.1734_1743dup (p.Pro582fs)	Pathogenic
1422433	NM_032888.4(COL27A1):c.2139T>A (p.Tyr713Ter)	Pathogenic
143245	NM_032888.4(COL27A1):c.2089G>C (p.Gly697Arg)	Pathogenic
1438526	NM_032888.4(COL27A1):c.2542del (p.Glu848fs)	Pathogenic
1451301	NM_032888.4(COL27A1):c.1373del (p.Ala458fs)	Pathogenic
1453215	NM_032888.4(COL27A1):c.3680_3692del (p.Asp1227fs)	Pathogenic
1453572	NM_032888.4(COL27A1):c.4760del (p.Pro1587fs)	Pathogenic
1454592	NM_032888.4(COL27A1):c.5373G>A (p.Trp1791Ter)	Pathogenic
1455677	NM_032888.4(COL27A1):c.4025del (p.Pro1342fs)	Pathogenic
1456974	NM_032888.4(COL27A1):c.490C>T (p.Arg164Ter)	Pathogenic
1458905	NM_032888.4(COL27A1):c.2065del (p.Ala689fs)	Pathogenic
1995366	NM_032888.4(COL27A1):c.1289del (p.Pro430fs)	Pathogenic
2002004	NM_032888.4(COL27A1):c.3377del (p.Gly1126fs)	Pathogenic
2014538	NM_032888.4(COL27A1):c.4560_4561del (p.Glu1521fs)	Pathogenic
2017061	NM_032888.4(COL27A1):c.3698dup (p.Gly1234fs)	Pathogenic
2019531	NM_032888.4(COL27A1):c.4729G>T (p.Gly1577Ter)	Pathogenic
2034642	NM_032888.4(COL27A1):c.4193C>A (p.Ser1398Ter)	Pathogenic
2034992	NM_032888.4(COL27A1):c.1865del (p.Leu622fs)	Pathogenic
2035776	NM_032888.4(COL27A1):c.3195+1G>A	Pathogenic
2036408	NM_032888.4(COL27A1):c.4114C>T (p.Gln1372Ter)	Pathogenic

SpliceAI

8588 predictions. Top by Δscore:

Variant	Effect	Δscore
9:114167686:CAG:C	acceptor_loss	1.0000
9:114167687:A:AG	acceptor_gain	1.0000
9:114167688:G:GT	acceptor_gain	1.0000
9:114167688:GAT:G	acceptor_gain	1.0000
9:114178289:AG:A	acceptor_gain	1.0000
9:114178290:GG:G	acceptor_gain	1.0000
9:114178343:GG:G	donor_gain	1.0000
9:114178343:GGGT:G	donor_loss	1.0000
9:114178344:GG:G	donor_gain	1.0000
9:114178345:G:GA	donor_loss	1.0000
9:114178345:G:GG	donor_gain	1.0000
9:114178346:TGA:T	donor_loss	1.0000
9:114178347:G:GT	donor_loss	1.0000
9:114183074:AA:A	donor_gain	1.0000
9:114183074:AAG:A	donor_loss	1.0000
9:114183075:AGT:A	donor_loss	1.0000
9:114183076:G:GG	donor_gain	1.0000
9:114183078:GAGTA:G	donor_loss	1.0000
9:114206295:GG:G	donor_gain	1.0000
9:114206296:GG:G	donor_gain	1.0000
9:114209518:GCC:G	donor_gain	1.0000
9:114209561:G:GT	donor_gain	1.0000
9:114209565:G:GT	donor_gain	1.0000
9:114209571:G:GT	donor_gain	1.0000
9:114209581:G:GT	donor_gain	1.0000
9:114209581:G:T	donor_gain	1.0000
9:114209670:CCTA:C	acceptor_loss	1.0000
9:114209672:TA:T	acceptor_loss	1.0000
9:114209673:A:AG	acceptor_gain	1.0000
9:114209673:AG:A	acceptor_gain	1.0000

AlphaMissense

11747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:114306649:T:A	C1690S	0.999
9:114306649:T:C	C1690R	0.999
9:114306650:G:A	C1690Y	0.999
9:114306650:G:C	C1690S	0.999
9:114306651:C:G	C1690W	0.999
9:114307725:T:A	C1722S	0.999
9:114307725:T:C	C1722R	0.999
9:114307726:G:A	C1722Y	0.999
9:114307726:G:C	C1722S	0.999
9:114306659:T:C	L1693P	0.998
9:114307727:C:G	C1722W	0.998
9:114309293:T:C	F1751L	0.998
9:114309295:C:A	F1751L	0.998
9:114309295:C:G	F1751L	0.998
9:114306596:T:C	L1672P	0.997
9:114307726:G:T	C1722F	0.997
9:114309303:T:C	L1754P	0.997
9:114306587:T:C	L1669P	0.996
9:114306650:G:T	C1690F	0.996
9:114309294:T:G	F1751C	0.996
9:114309308:A:C	S1756R	0.996
9:114309310:C:A	S1756R	0.996
9:114309310:C:G	S1756R	0.996
9:114309405:T:C	F1788S	0.996
9:114307674:T:G	Y1705D	0.995
9:114307732:T:G	F1724C	0.995
9:114309294:T:C	F1751S	0.995
9:114309473:T:A	C1811S	0.995
9:114309474:G:C	C1811S	0.995
9:114307684:A:G	D1708G	0.994

dbSNP variants (sampled 300 via entrez): RS1000004375 (9:114204751 T>C), RS1000021744 (9:114171030 G>A), RS1000039044 (9:114234937 G>A), RS1000050541 (9:114245380 C>T), RS1000052829 (9:114170736 G>A), RS1000084137 (9:114249060 G>A,T), RS1000088625 (9:114215583 A>G), RS1000119198 (9:114277727 G>A), RS1000128053 (9:114291703 C>T), RS1000139138 (9:114304475 G>C), RS1000191472 (9:114228097 C>T), RS1000210681 (9:114201188 C>T), RS1000217990 (9:114260672 AGG>A), RS1000247916 (9:114307424 C>T), RS1000290704 (9:114299358 A>G)

Disease associations

OMIM: gene MIM:608461 | disease phenotypes: MIM:615155

GenCC curated gene-disease

Disease	Classification	Inheritance
Steel syndrome	Definitive	Autosomal recessive

Mondo (1): Steel syndrome (MONDO:0014061)

Orphanet (1): Steel syndrome (Orphanet:438117)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000316	Hypertelorism
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0001263	Global developmental delay
HP:0001377	Limited elbow extension
HP:0001761	Pes cavus
HP:0001763	Pes planus
HP:0002650	Scoliosis
HP:0002812	Coxa vara
HP:0002827	Hip dislocation
HP:0002938	Lumbar hyperlordosis
HP:0003083	Dislocated radial head
HP:0003593	Infantile onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0009702	Carpal synostosis
HP:0011220	Prominent forehead
HP:0011463	Childhood onset
HP:0011800	Midface retrusion

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000175_41	Height	2.000000e-07
GCST001635_1	Tourette syndrome	3.000000e-08
GCST002367_1	Social communication problems	6.000000e-06
GCST008363_70	Offspring birth weight	4.000000e-15
GCST008672_1	Knee pain	2.000000e-08
GCST008672_2	Knee pain	1.000000e-08
GCST90000025_420	Appendicular lean mass	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364188 (PROTEIN COMPLEX GROUP)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression, decreases expression	3
bisphenol A	affects expression, affects cotreatment, increases methylation, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
dicrotophos	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	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
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Cannabinoids	affects methylation, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Paraquat	increases expression, increases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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