SMOC1

Summary

SMOC1 (SPARC related modular calcium binding 1, HGNC:20318) is a protein-coding gene on chromosome 14q24.1, encoding SPARC-related modular calcium-binding protein 1 (Q9H4F8). Plays essential roles in both eye and limb development.

This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 64093 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microphthalmia with limb anomalies (Definitive, GenCC)
• GWAS associations: 25
• Clinical variants (ClinVar): 155 total — 9 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 82
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001034852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20318
Approved symbol	SMOC1
Name	SPARC related modular calcium binding 1
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198732
Ensembl biotype	protein_coding
OMIM	608488
Entrez	64093

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000361956, ENST00000381280, ENST00000553839, ENST00000555917, ENST00000557483, ENST00000853903, ENST00000853904, ENST00000853905, ENST00000853906, ENST00000853907, ENST00000853908, ENST00000853909, ENST00000853910, ENST00000853911, ENST00000853912

RefSeq mRNA: 4 — MANE Select: NM_001034852 NM_001034852, NM_001425244, NM_001425245, NM_022137

CCDS: CCDS32110, CCDS9798

Canonical transcript exons

ENST00000361956 — 12 exons

Exon	Start	End
ENSE00000911680	69977918	69977965
ENSE00000911682	69992417	69992473
ENSE00000911684	69994400	69994480
ENSE00000911688	70011485	70011567
ENSE00000911690	70013386	70013491
ENSE00001167484	70023203	70023447
ENSE00001215769	70030242	70032366
ENSE00002536421	69879416	69879777
ENSE00003480376	70010754	70010946
ENSE00003564364	69975715	69975814
ENSE00003647558	69953420	69953532
ENSE00003664610	69952138	69952303

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 95.46.

FANTOM5 (CAGE): breadth broad, TPM avg 17.2720 / max 889.2839, expressed in 892 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140388	17.1972	892
140394	0.0748	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	95.46	gold quality
inferior vagus X ganglion	UBERON:0005363	93.78	gold quality
right lobe of liver	UBERON:0001114	93.25	gold quality
tendon of biceps brachii	UBERON:0008188	93.23	gold quality
liver	UBERON:0002107	91.77	gold quality
corpus callosum	UBERON:0002336	91.68	gold quality
substantia nigra	UBERON:0002038	91.67	gold quality
amygdala	UBERON:0001876	91.58	gold quality
midbrain	UBERON:0001891	91.31	gold quality
medial globus pallidus	UBERON:0002477	91.16	gold quality
islet of Langerhans	UBERON:0000006	90.86	gold quality
popliteal artery	UBERON:0002250	90.58	gold quality
tibial artery	UBERON:0007610	90.53	gold quality
ventral tegmental area	UBERON:0002691	90.45	gold quality
globus pallidus	UBERON:0001875	90.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.18	gold quality
right testis	UBERON:0004534	89.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.67	gold quality
spinal cord	UBERON:0002240	89.66	gold quality
Ammon’s horn	UBERON:0001954	89.28	gold quality
hypothalamus	UBERON:0001898	89.25	gold quality
left testis	UBERON:0004533	89.19	gold quality
subthalamic nucleus	UBERON:0001906	89.02	gold quality
testis	UBERON:0000473	88.47	gold quality
substantia nigra pars compacta	UBERON:0001965	88.46	gold quality
temporal lobe	UBERON:0001871	88.13	gold quality
medulla oblongata	UBERON:0001896	88.01	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.53	gold quality
superior vestibular nucleus	UBERON:0007227	87.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.29	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	74.35
E-GEOD-84465	yes	27.93
E-MTAB-5061	yes	25.64
E-HCAD-25	yes	20.74
E-GEOD-81608	yes	15.39
E-ENAD-27	yes	11.49
E-GEOD-83139	yes	10.39
E-GEOD-93593	yes	5.09
E-ANND-3	no	4.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BGLAP	Activation
COL1A1	Activation
COL1A2	Activation
SPARC	Activation
SPP1	Activation

miRNA regulators (miRDB)

144 targeting SMOC1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-454-3P	99.91	74.01	1925

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 17)

• isolation of the novel gene SMOC-1 encoding a secreted modular protein containing an EF-hand calcium-binding domain; localization within basement membranes in kidney and skeletal muscle and expression in the zona pellucida surrounding the oocyte (PMID:12130637)
• SMOC-1 is of physiological interest because it codes a secreted glycoprotein with five domains, each containing regions homologous to those on other proteins that mediate cell-matrix interactions. (PMID:17386346)
• Analyzed the secretory protein profiles of BMSCs grown in osteogenic medium (OSM) and identified SPARC-related modular calcium-binding protein 1 (SMOC1), a member of the SPARC family, as a regulator of osteoblast differentiation of BMSCs. (PMID:20359165)
• these findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice. (PMID:21194678)
• Waardenburg anophthalmia syndrome is genetically heterogeneous; a second was locus found on chromosome 14, and mutations in SMOC1 were shown also cause this syndrome. (PMID:21194680)
• The present study thus identified SPARC related modular calcium binding 1 as a new cancer-associated protein capable of interacting with tenascin-C in vitro (PMID:21349332)
• Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families with Waardenburg Anophthalmia syndrome. (PMID:21750680)
• SMOC1 provides a link between prenatal hormone exposure and digit ratio. (PMID:23263445)
• IL-17A but not IL-22 suppresses the replication of hepatitis B virus by inducing the expression of MxA and OAS. (PMID:23274784)
• SMOC binds to Pro-EGF, but does not induce Erk phosphorylation via the EGFR. (PMID:27101391)
• This is the first report of Waardenburg anophthalmia syndrome (WAS) caused by a SMOC1 variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SMOC-1 in causing WAS. (PMID:28085523)
• Missense mutation in exon 3 of SMOC1 segregated with the Waardenburg anophthalmia syndrome in the Iranian family. (PMID:28807869)
• Exome sequencing identified two variants in the SMOC1 gene, each inherited from one of the parents: c.709G>T - p.(Glu237*) on exon 8 and c.1223G>A - p.(Cys408Tyr) on exon 11, both predicted to be pathogenic by different bioinformatics software. Brain histopathology showed an abnormal cortical neuronal migration, which could be related to the SMOC1 protein function, given its role in cellular signaling (PMID:30445150)
• SMOC1 and IL-4 and IL-13 Cytokines Interfere with Ca(2+) Mobilization in Primary Human Keratinocytes. (PMID:33484701)
• Secreted modular calcium-binding protein 1 binds and activates thrombin to account for platelet hyperreactivity in diabetes. (PMID:33529332)
• SPARC-related modular calcium binding 1 regulates aortic valve calcification by disrupting BMPR-II/p-p38 signalling. (PMID:33757126)
• Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas. (PMID:38429655)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smoc1	ENSDARG00000088255
mus_musculus	Smoc1	ENSMUSG00000021136
rattus_norvegicus	Smoc1	ENSRNOG00000005998
drosophila_melanogaster	magu	FBGN0262169
caenorhabditis_elegans		WBGENE00011437

Paralogs (1): SMOC2 (ENSG00000112562)

Protein

Protein identifiers

SPARC-related modular calcium-binding protein 1 — Q9H4F8 (reviewed: Q9H4F8)

Alternative names: Secreted modular calcium-binding protein 1

All UniProt accessions (1): Q9H4F8

UniProt curated annotations — full annotation on UniProt →

Function. Plays essential roles in both eye and limb development. Probable regulator of osteoblast differentiation.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Tissue specificity. Widely expressed in many tissues with a strongest signal in ovary. No expression in spleen.

Post-translational modifications. Glycosylated.

Disease relevance. Ophthalmoacromelic syndrome (OAS) [MIM:206920] A rare disorder presenting with ocular anomalies, ranging from mild microphthalmia to true anophthalmia, and limb anomalies. Limb malformations include fused 4th and 5th metacarpals and short 5th finger in hands, and oligodactyly in foot (four toes). Most patients have bilateral anophthalmia/ microphthalmia, but unilateral abnormality is also noted. Other malformations are rare, but venous or vertebral anomaly was recognized each in single cases. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H4F8-1	1	yes
Q9H4F8-2	2

RefSeq proteins (4): NP_001030024, NP_001412173, NP_001412174, NP_071420 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR002350	Kazal_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR019577	SPARC/Testican_Ca-bd-dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily
IPR037639	SMOC1_EC	Domain
IPR051950	Dev_reg/Prot_inhib	Family

Pfam: PF00086, PF07648, PF10591, PF16597

UniProt features (34 total): binding site 9, disulfide bond 9, domain 5, sequence variant 4, glycosylation site 2, signal peptide 1, chain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4F8-F1	73.69	0.27

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 (9): 374; 376; 378; 383; 409; 411; 413; 420; 372

Disulfide bonds (9): 43–74, 47–67, 56–87, 95–118, 129–136, 138–158, 227–251, 262–269, 271–292

Glycosylation sites (2): 214, 374

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 370 (showing top): RNGTGGGC_UNKNOWN, CREL_01, MYOGENIN_Q6, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, GOBP_OSTEOBLAST_DIFFERENTIATION, TGACCTY_ERR1_Q2, GTACAGG_MIR486, COUP_01, NFKB_C, CDP_01, chr14q24, GOBP_APPENDAGE_DEVELOPMENT, HNF4_DR1_Q3, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP

GO Biological Process (5): eye development (GO:0001654), cell differentiation (GO:0030154), extracellular matrix organization (GO:0030198), regulation of osteoblast differentiation (GO:0045667), limb development (GO:0060173)

GO Molecular Function (5): calcium ion binding (GO:0005509), heparin binding (GO:0008201), extracellular matrix binding (GO:0050840), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
sensory organ development	1
visual system development	1
cellular developmental process	1
extracellular structure organization	1
external encapsulating structure organization	1
osteoblast differentiation	1
regulation of cell differentiation	1
appendage development	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
cation binding	1
extracellular matrix	1
cellular anatomical structure	1

Protein interactions and networks

STRING

970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMOC1	SPARC	P09486	820
SMOC1	FST	P19883	782
SMOC1	SFMBT2	Q5VUG0	628
SMOC1	SLC38A4	Q969I6	606
SMOC1	JADE1	Q6IE81	592
SMOC1	SPOCK1	Q08629	500
SMOC1	FKBP10	Q96AY3	477
SMOC1	CLDN14	O95500	477
SMOC1	CLEC3B	P05452	474
SMOC1	LGI2	Q8N0V4	464
SMOC1	SALL1	Q9NSC2	462
SMOC1	FBLN2	P98095	455
SMOC1	SPARCL1	Q14515	444
SMOC1	TOX3	O15405	443
SMOC1	FLNA	P21333	442

IntAct

43 interactions, top by confidence:

A	B	Type	Score
SMOC1	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
NOTCH2NLA	SMOC1	psi-mi:“MI:0915”(physical association)	0.670
TCF4	SMOC1	psi-mi:“MI:0915”(physical association)	0.560
SMOC1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
	SMOC1	psi-mi:“MI:0915”(physical association)	0.560
SMOC1	TCF4	psi-mi:“MI:0915”(physical association)	0.560
SMOC1		psi-mi:“MI:0915”(physical association)	0.560
	PLOD2	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
Hoxa1	SMOC1	psi-mi:“MI:0915”(physical association)	0.510
SMOC1	Hoxa1	psi-mi:“MI:0915”(physical association)	0.510
SMOC1	ORF7a	psi-mi:“MI:0915”(physical association)	0.370
TNIP1	COCH	psi-mi:“MI:0914”(association)	0.350
TNIP2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
RNPS1	C1orf226	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
GINM1	FAM234B	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
DKK3	MYO9A	psi-mi:“MI:0914”(association)	0.350
PATE1	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): SMOC1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), SMOC1 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), Hoxa1 (Affinity Capture-Western), SMOC1 (Affinity Capture-MS), NME2 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), NAF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A5PMY6, A8WGB1, B4HVU2, B4IXJ2, B4PD96, B4QMF4, D3YXF5, O18738, O35167, O35251, O35348, O43278, O43915, O75339, O89103, P06213, P10643, P13385, P21757, P21758, P51864, P51865, P97946, Q03637, Q05585, Q29243, Q3MI99, Q4LDE5, Q4ZJM7, Q58T08, Q5G872, Q5RAD0, Q5RBP1, Q62165, Q66K08, Q6NZL8, Q6UXH8, Q6UXI9, Q76LD0

Diamond homologs: A0A1D0C023, B3F211, B5DFC9, P04233, P04441, P10247, P10493, P31226, P81439, P84032, Q08629, Q14112, Q62288, Q8BKV0, Q8BLY1, Q8CD91, Q92563, Q9ER58, Q9H3U7, Q9H4F8, A0A060S684, A0A0E4AET8, A0A8B0RBM2, A2AVA0, A7YN26, B2D0J5, D2D3B6, D4AZ78, D6WMZ8, F1RRV3, I1RHF8, O08710, O16168, O16169, O16170, O16171, O16172, O16173, O62760, O62761

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SMOC1	“up-regulates quantity by expression”	SPP1	“transcriptional regulation”
SMOC1	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
SMOC1	“up-regulates quantity by expression”	SPARC	“transcriptional regulation”
SMOC1	“up-regulates quantity by expression”	COL1A1	“transcriptional regulation”
SMOC1	“up-regulates quantity by expression”	COL1A2	“transcriptional regulation”
SMOC1	“up-regulates quantity”	Angiotensin-2

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	4
Uncertain significance	63
Likely benign	37
Benign	28

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1323630	NM_001034852.3(SMOC1):c.482C>A (p.Ser161Ter)	Pathogenic
2033665	NM_001034852.3(SMOC1):c.445del (p.Ser149fs)	Pathogenic
2736124	NM_001034852.3(SMOC1):c.274C>T (p.Gln92Ter)	Pathogenic
3026644	NM_001034852.3(SMOC1):c.661del (p.Ser221fs)	Pathogenic
30727	NM_001034852.3(SMOC1):c.664+1G>A	Pathogenic
30728	NM_001034852.3(SMOC1):c.378+1G>A	Pathogenic
427815	NM_001034852.3(SMOC1):c.367T>C (p.Ser123Pro)	Pathogenic
562135	NM_001034852.3(SMOC1):c.378+1G>T	Pathogenic
599220	NM_001034852.3(SMOC1):c.223C>T (p.Arg75Ter)	Pathogenic
1325107	NM_001034852.3(SMOC1):c.584-2A>G	Likely pathogenic
3777060	NM_001034852.3(SMOC1):c.406T>G (p.Cys136Gly)	Likely pathogenic
4292147	NM_001034852.3(SMOC1):c.230del (p.Pro77fs)	Likely pathogenic
562134	NM_001034852.3(SMOC1):c.1223G>A (p.Cys408Tyr)	Likely pathogenic

SpliceAI

2905 predictions. Top by Δscore:

Variant	Effect	Δscore
14:69879776:GG:G	donor_gain	1.0000
14:69879777:GG:G	donor_gain	1.0000
14:69879778:G:GG	donor_gain	1.0000
14:69879779:T:G	donor_loss	1.0000
14:69953417:CAG:C	acceptor_loss	1.0000
14:69953418:A:AG	acceptor_gain	1.0000
14:69953418:AGA:A	acceptor_loss	1.0000
14:69953418:AGAT:A	acceptor_gain	1.0000
14:69953419:G:GG	acceptor_gain	1.0000
14:69953419:GA:G	acceptor_gain	1.0000
14:69953419:GAT:G	acceptor_gain	1.0000
14:69953419:GATG:G	acceptor_gain	1.0000
14:69953419:GATGC:G	acceptor_gain	1.0000
14:69953485:G:GT	donor_gain	1.0000
14:69953528:CCCAG:C	donor_loss	1.0000
14:69953529:CCAGG:C	donor_loss	1.0000
14:69953530:CAGGT:C	donor_loss	1.0000
14:69953531:AGG:A	donor_loss	1.0000
14:69953532:GGTGA:G	donor_loss	1.0000
14:69953533:G:A	donor_loss	1.0000
14:69953534:T:A	donor_loss	1.0000
14:69994477:TCAGG:T	donor_loss	1.0000
14:69994478:CAGGT:C	donor_loss	1.0000
14:69994480:GGT:G	donor_loss	1.0000
14:69994481:G:GC	donor_loss	1.0000
14:69994482:T:A	donor_loss	1.0000
14:70010752:A:AG	acceptor_gain	1.0000
14:70010753:G:GG	acceptor_gain	1.0000
14:70010753:GA:G	acceptor_gain	1.0000
14:70011557:G:GT	donor_gain	1.0000

AlphaMissense

2843 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:69952204:T:A	C56S	1.000
14:69952205:G:C	C56S	1.000
14:69953437:T:A	C95S	1.000
14:69953437:T:C	C95R	1.000
14:69953438:G:C	C95S	1.000
14:69953495:T:G	F114C	1.000
14:69953506:T:A	C118S	1.000
14:69953506:T:C	C118R	1.000
14:69953507:G:C	C118S	1.000
14:69975721:T:A	C129S	1.000
14:69975722:G:C	C129S	1.000
14:69975742:T:A	C136S	1.000
14:69975742:T:C	C136R	1.000
14:69975743:G:A	C136Y	1.000
14:69975743:G:C	C136S	1.000
14:69975744:C:G	C136W	1.000
14:69975745:T:A	W137R	1.000
14:69975745:T:C	W137R	1.000
14:69975747:G:C	W137C	1.000
14:69975747:G:T	W137C	1.000
14:69975748:T:A	C138S	1.000
14:69975748:T:C	C138R	1.000
14:69975749:G:C	C138S	1.000
14:69975750:T:G	C138W	1.000
14:69975763:G:T	G143W	1.000
14:69975764:G:A	G143E	1.000
14:69975764:G:T	G143V	1.000
14:69975808:T:A	C158S	1.000
14:69975808:T:C	C158R	1.000
14:69975809:G:C	C158S	1.000

dbSNP variants (sampled 300 via entrez): RS1000008772 (14:69922589 A>G), RS1000057419 (14:69937301 G>C,T), RS1000090763 (14:69963839 C>T), RS1000095213 (14:69970418 T>C), RS1000112466 (14:69948507 C>T), RS1000130679 (14:69987951 A>G), RS1000165461 (14:69952913 T>C), RS1000192702 (14:69903519 A>T), RS1000192835 (14:70031073 A>G), RS1000195631 (14:69912704 T>C), RS1000221685 (14:69914819 G>T), RS1000226355 (14:69922920 G>A), RS1000262109 (14:69953084 G>T), RS1000263482 (14:69957185 C>A), RS1000284016 (14:69880733 C>T)

Disease associations

OMIM: gene MIM:608488 | disease phenotypes: MIM:206920

GenCC curated gene-disease

Disease	Classification	Inheritance
microphthalmia with limb anomalies	Definitive	Autosomal recessive

Mondo (1): microphthalmia with limb anomalies (MONDO:0008800)

Orphanet (1): Microphthalmia with limb anomalies (Orphanet:1106)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000085	Horseshoe kidney
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000278	Retrognathia
HP:0000327	Hypoplasia of the maxilla
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000454	Flared nostrils
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000528	Anophthalmia
HP:0000534	Abnormal eyebrow morphology
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000648	Optic atrophy
HP:0000954	Single transverse palmar crease
HP:0000960	Sacral dimple
HP:0001162	Postaxial hand polydactyly
HP:0001172	Abnormal thumb morphology
HP:0001215	Camptodactyly of 2nd-5th fingers
HP:0001241	Capitate-hamate fusion
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001765_14	Red blood cell traits	1.000000e-09
GCST002198_9	Tuberculosis	9.000000e-09
GCST002276_17	Bone mineral density	4.000000e-13
GCST002276_21	Bone mineral density	2.000000e-06
GCST002276_22	Bone mineral density	4.000000e-07
GCST002276_23	Bone mineral density	1.000000e-06
GCST003518_91	Daytime sleep phenotypes	2.000000e-06
GCST004621_70	Red cell distribution width	3.000000e-15
GCST004630_152	Mean corpuscular hemoglobin	2.000000e-11
GCST005748_7	Digit length ratio (right hand)	2.000000e-11
GCST005749_18	Digit length ratio (left hand)	3.000000e-22
GCST005749_3	Digit length ratio (left hand)	5.000000e-23
GCST005750_8	Digit length ratio	2.000000e-17
GCST006436_13	Triglyceride levels	1.000000e-09
GCST006585_349	Blood protein levels	2.000000e-15
GCST006585_674	Blood protein levels	4.000000e-06
GCST006979_1007	Heel bone mineral density	9.000000e-10
GCST008474_17	Peripheral artery disease	3.000000e-08
GCST008514_21	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	7.000000e-06
GCST010002_155	Refractive error	6.000000e-11
GCST90000025_540	Appendicular lean mass	4.000000e-40
GCST90000025_541	Appendicular lean mass	1.000000e-24
GCST90002390_270	Mean corpuscular hemoglobin	8.000000e-23
GCST90002392_458	Mean corpuscular volume	1.000000e-18
GCST90002404_396	Red cell distribution width	2.000000e-20

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004841	digit length ratio
EFO:0004530	triglyceride measurement
EFO:0009270	heel bone mineral density
EFO:0010103	response to peginterferon alfa-2a
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537769	Anophthalmos with limb anomalies (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	8
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	decreases expression	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	increases expression, affects cotreatment	2
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
belinostat	decreases expression, affects cotreatment	2
Vorinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, affects expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	increases methylation	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
cupric chloride	increases expression	1
diallyl trisulfide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7DT	HeLa SMOC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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