NADSYN1

Summary

NADSYN1 (NAD synthetase 1, HGNC:29832) is a protein-coding gene on chromosome 11q13.4, encoding Glutamine-dependent NAD(+) synthetase (Q6IA69). Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic redox reactions, a precursor for several cell signaling molecules, and a substrate for protein posttranslational modifications. NAD synthetase (EC 6.3.5.1) catalyzes the final step in the biosynthesis of NAD from nicotinic acid adenine dinucleotide (NaAD).

Source: NCBI Gene 55191 — RefSeq curated summary.

At a glance

• Gene–disease (curated): vertebral, cardiac, renal, and limb defects syndrome 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 177 total — 7 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_018161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29832
Approved symbol	NADSYN1
Name	NAD synthetase 1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10631
Ensembl gene	ENSG00000172890
Ensembl biotype	protein_coding
OMIM	608285
Entrez	55191

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 10 protein_coding, 8 retained_intron, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 1 TEC

ENST00000319023, ENST00000524450, ENST00000524949, ENST00000525200, ENST00000525245, ENST00000525593, ENST00000526039, ENST00000527227, ENST00000527538, ENST00000527852, ENST00000527963, ENST00000528211, ENST00000528509, ENST00000529120, ENST00000529840, ENST00000530055, ENST00000530534, ENST00000530831, ENST00000531236, ENST00000533612, ENST00000533769, ENST00000534634, ENST00000624637, ENST00000859578, ENST00000859579, ENST00000859580, ENST00000859581, ENST00000935794, ENST00000935795, ENST00000935796

RefSeq mRNA: 1 — MANE Select: NM_018161 NM_018161

CCDS: CCDS8201

Canonical transcript exons

ENST00000319023 — 21 exons

Exon	Start	End
ENSE00001219925	71473569	71473686
ENSE00001219930	71473278	71473366
ENSE00002192165	71501302	71501816
ENSE00003481741	71482849	71483017
ENSE00003487602	71497483	71497611
ENSE00003491583	71472449	71472500
ENSE00003521012	71490845	71490976
ENSE00003522327	71458428	71458544
ENSE00003530850	71484312	71484447
ENSE00003531596	71464053	71464142
ENSE00003549810	71481923	71482025
ENSE00003560530	71463432	71463485
ENSE00003592886	71481356	71481404
ENSE00003600208	71478395	71478469
ENSE00003624040	71498352	71498528
ENSE00003631393	71453203	71453381
ENSE00003661600	71474395	71474526
ENSE00003668161	71480755	71480879
ENSE00003673800	71455110	71455170
ENSE00003679969	71491834	71491903
ENSE00003787070	71485542	71485648

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1764 / max 247.1612, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115686	37.3356	1825
115687	0.3190	125
115685	0.3064	128
115684	0.1476	71
206369	0.0678	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.98	gold quality
granulocyte	CL:0000094	97.87	gold quality
mucosa of transverse colon	UBERON:0004991	97.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.49	gold quality
transverse colon	UBERON:0001157	97.31	gold quality
lower esophagus mucosa	UBERON:0035834	97.26	gold quality
esophagus mucosa	UBERON:0002469	96.60	gold quality
adenohypophysis	UBERON:0002196	96.56	gold quality
minor salivary gland	UBERON:0001830	96.28	gold quality
left ovary	UBERON:0002119	96.23	gold quality
right lung	UBERON:0002167	96.20	gold quality
skin of leg	UBERON:0001511	96.17	gold quality
rectum	UBERON:0001052	96.16	gold quality
esophagus	UBERON:0001043	96.11	gold quality
body of stomach	UBERON:0001161	96.08	gold quality
right lobe of thyroid gland	UBERON:0001119	96.05	gold quality
right ovary	UBERON:0002118	96.05	gold quality
small intestine	UBERON:0002108	96.04	gold quality
left uterine tube	UBERON:0001303	96.01	gold quality
spleen	UBERON:0002106	95.96	gold quality
left lobe of thyroid gland	UBERON:0001120	95.93	gold quality
skin of abdomen	UBERON:0001416	95.88	gold quality
lower esophagus	UBERON:0013473	95.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.81	gold quality
gall bladder	UBERON:0002110	95.78	gold quality
body of uterus	UBERON:0009853	95.69	gold quality
upper lobe of left lung	UBERON:0008952	95.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.63	gold quality
metanephros cortex	UBERON:0010533	95.60	gold quality
endocervix	UBERON:0000458	95.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting NADSYN1, 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-8075	99.97	67.20	962
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-2682-3P	97.10	66.16	840

Literature-anchored findings (GeneRIF, showing 12)

• several SNPs related to calcium metabolism are associated with height, in particular rs3829251 at the DHCR7/NADSYN1 gene. (PMID:22390397)
• findings suggest that VDR, NADSYN1, and GC polymorphisms may be linked to the manifestation of vitamin D deficiency in Japanese children (PMID:22785457)
• Data indicate that SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with rheumatoid arthritis (RA). (PMID:23636220)
• NADSYN1/DHCR7 locus (rs12785878 and rs1790349) polymorphisms have an effect on plasma 25-hydroxyvitamin D levels and coronary artery disease incidence (PMID:24642724)
• Polymorphisms in CYP2R1-rs10766197 and DHCR7/NADSYN1-rs12785878 are associated with vitamin D deficiency in Uygur and Kazak ethnic populations (PMID:26149120)
• Bi-allelic Mutations in NADSYN1 Cause Multiple Organ Defects and Expand the Genotypic Spectrum of Congenital NAD Deficiency Disorders. (PMID:31883644)
• Homo sapiens NAD(+) synthetase (hsNadE) lacks substrate specificity for glutamine over ammonia. (PMID:31911602)
• Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson’s disease. (PMID:32938288)
• Disruptive NADSYN1 Variants Implicated in Congenital Vertebral Malformations. (PMID:34681008)
• Further description of two patients with biallelic variants in NADSYN1 in association with cardiac and vertebral anomalies. (PMID:35491967)
• Clinical heterogeneity of NADSYN1-associated VCRL syndrome. (PMID:36951206)
• A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder. (PMID:38357931)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nadsyn1	ENSDARG00000101378
mus_musculus	Nadsyn1	ENSMUSG00000031090
rattus_norvegicus	Nadsyn1	ENSRNOG00000020736
drosophila_melanogaster	Nadsyn	FBGN0030512
caenorhabditis_elegans		WBGENE00007698

Protein

Protein identifiers

Glutamine-dependent NAD(+) synthetase — Q6IA69 (reviewed: Q6IA69)

Alternative names: NAD(+) synthase [glutamine-hydrolyzing], NAD(+) synthetase

All UniProt accessions (9): A0A0B4J216, E9PKY6, E9PND0, E9PNF5, Q6IA69, H0YCF9, H0YCQ6, H0YDH3, H0YED2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source.

Subunit / interactions. Homohexamer.

Disease relevance. Vertebral, cardiac, renal, and limb defects syndrome 3 (VCRL3) [MIM:618845] An autosomal recessive, lethal disorder characterized by severe cardiac and renal anomalies, including hypoplastic or absent left ventricle, transposition of the great arteries, absent pulmonary trunk, and hypoplastic or absent kidneys. Patients also exhibit vertebral segmentation defects and shortening of the proximal long bones or micromelia. Death occurs in early infancy. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from deamido-NAD(+) (L-Gln route): step 1/1.

Similarity. In the C-terminal section; belongs to the NAD synthetase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IA69-1	1	yes
Q6IA69-2	2

RefSeq proteins (1): NP_060631* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003010	C-N_Hydrolase	Domain
IPR003694	NAD_synthase	Family
IPR014445	Gln-dep_NAD_synthase	Family
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR022310	NAD/GMP_synthase	Domain
IPR036526	C-N_Hydrolase_sf	Homologous_superfamily

Pfam: PF00795, PF02540

Enzyme classification (BRENDA):

• EC 6.3.5.1 — NAD+ synthase (glutamine-hydrolysing) (BRENDA: 12 organisms, 18 substrates, 15 inhibitors, 77 Km, 33 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DEAMIDO-NAD+	0.01–2.9	19
ATP	0.015–1.4	18
L-GLUTAMINE	0.08–8.3	12
NH4+	0.24–64.2	10
L-GLN	0.001–20	6
NH3	0.089–42	6
GLN	2–5	3
DEAMIDO-NMN	4.3	1

Catalyzed reactions (Rhea), 1 shown:

• deamido-NAD(+) + L-glutamine + ATP + H2O = L-glutamate + AMP + diphosphate + NAD(+) + H(+) (RHEA:24384)

UniProt features (76 total): helix 28, strand 21, sequence variant 10, active site 4, sequence conflict 3, turn 3, splice variant 2, chain 1, domain 1, region of interest 1, mutagenesis site 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6OFB	X-RAY DIFFRACTION	2.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IA69-F1	96.11	0.93

Functional residue map

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

Catalytic / active sites (4): 45 (proton acceptor; for glutaminase activity); 114 (for glutaminase activity); 175 (nucleophile; for glutaminase activity); 357

Ligand- & substrate-binding residues (1): 355–362

Mutagenesis-validated functional residues (1):

Position	Phenotype
175	eliminates glutamine-dependent nad synthetase activity with the ammonia-dependent activity intact.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 162 (showing top): WANG_CLIM2_TARGETS_UP, MODULE_255, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MENSE_HYPOXIA_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, chr11q13, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS

GO Biological Process (3): NAD+ biosynthetic process (GO:0009435), ‘de novo’ NAD+ biosynthetic process from L-tryptophan (GO:0034354), NAD+ biosynthetic process via the salvage pathway (GO:0034355)

GO Molecular Function (6): NAD+ synthase (glutamine-hydrolyzing) activity (GO:0003952), glutaminase activity (GO:0004359), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
NAD+ biosynthetic process	2
cellular anatomical structure	2
purine nucleotide biosynthetic process	1
nicotinamide nucleotide biosynthetic process	1
NAD+ metabolic process	1
aromatic amino acid metabolic process	1
indole-containing compound metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
carbon-nitrogen ligase activity, with glutamine as amido-N-donor	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NADSYN1	CYP2R1	Q6VVX0	840
NADSYN1	DHCR7	Q9UBM7	818
NADSYN1	CYP24A1	Q07973	717
NADSYN1	NAPRT	Q6XQN6	709
NADSYN1	NMRK1	Q9NWW6	709
NADSYN1	NMNAT1	Q9HAN9	675
NADSYN1	GC	P02774	669
NADSYN1	QPRT	Q15274	667
NADSYN1	AMDHD1	Q96NU7	660
NADSYN1	C10orf88	Q9H8K7	655
NADSYN1	A0A2R8YFG2	A0A2R8YFG2	619
NADSYN1	NMRK2	Q9NPI5	616
NADSYN1	HAAO	P46952	593
NADSYN1	NADK	O95544	576
NADSYN1	CYP27B1	O15528	574

IntAct

65 interactions, top by confidence:

A	B	Type	Score
EMC2	EMC8	psi-mi:“MI:0914”(association)	0.940
MMGT1	EMC8	psi-mi:“MI:0914”(association)	0.730
NADSYN1	CUTC	psi-mi:“MI:0915”(physical association)	0.670
AIPL1	PDE5A	psi-mi:“MI:0914”(association)	0.640
NADSYN1		psi-mi:“MI:0915”(physical association)	0.560
	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
MYO15B	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
HGS	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
CREB5	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
NADSYN1	NOXA1	psi-mi:“MI:0915”(physical association)	0.560
NADSYN1	TFG	psi-mi:“MI:0915”(physical association)	0.560
NADSYN1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
FRS3	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
ANKS1A	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	NADSYN1	psi-mi:“MI:0915”(physical association)	0.560
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
EMC6	EMC8	psi-mi:“MI:0914”(association)	0.530
STUB1	DNAJC13	psi-mi:“MI:0914”(association)	0.530
FKBPL	BRAF	psi-mi:“MI:0914”(association)	0.530
STUB1	DNAJB6	psi-mi:“MI:0914”(association)	0.530
NADSYN1	PARP1	psi-mi:“MI:0915”(physical association)	0.400
NADSYN1	THOC2	psi-mi:“MI:0915”(physical association)	0.400
CUTC	NADSYN1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (49): MYO15B (Two-hybrid), NADSYN1 (Two-hybrid), MYO15B (Two-hybrid), NADSYN1 (Affinity Capture-MS), NADSYN1 (Affinity Capture-MS), NADSYN1 (Affinity Capture-MS), NADSYN1 (Affinity Capture-RNA), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid), NADSYN1 (Two-hybrid)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, A4FV08, A4IHW6, O15305, O35621, O80840, O88958, O97555, O97556, P21856, P31150, P38024, P46926, P50395, P50396, P50397, P50398, P50399, P60028, Q1W374, Q1W375, Q1W376, Q1W377, Q259G4, Q3SZJ9, Q42521, Q4R5Y2, Q5E982, Q5R8T8, Q5RCE1, Q5ZID6, Q5ZJL4, Q60HD6, Q61598, Q64422, Q6IA69, Q6PA43, Q6Q7J2

Diamond homologs: A2YII8, A3DP41, A5IU80, A6QIE0, A6U318, A7X442, A8A0T1, A8Z2S7, B1IPJ0, B1XGK1, B2U3C0, B8D778, B8D8X4, C4ZZ96, C6A5B5, C6DFZ6, O74940, P18843, P38795, P57271, P65506, P65507, P99150, Q0AX10, Q0D8D4, Q2FFI3, Q2G236, Q2NRT4, Q2YU60, Q321N2, Q3B5D4, Q3ZBF0, Q4R5Y2, Q54ML1, Q5HEK9, Q5HN23, Q5ZMA6, Q65RB5, Q6D4H8, Q6G820

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	106
Likely benign	9
Benign	15

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1176583	NM_018161.5(NADSYN1):c.86-2A>C	Pathogenic
3351528	NM_018161.5(NADSYN1):c.85+1G>C	Pathogenic
4527052	NM_018161.5(NADSYN1):c.862C>T (p.Arg288Ter)	Pathogenic
834711	NM_018161.5(NADSYN1):c.1819del (p.Val607fs)	Pathogenic
834713	NM_018161.5(NADSYN1):c.735T>A (p.Cys245Ter)	Pathogenic
834715	NM_018161.5(NADSYN1):c.1839C>G (p.Tyr613Ter)	Pathogenic
869157	NM_018161.5(NADSYN1):c.145T>C (p.Cys49Arg)	Pathogenic
2575904	NM_018161.5(NADSYN1):c.1088C>T (p.Ala363Val)	Likely pathogenic
3382592	NM_018161.5(NADSYN1):c.1744C>T (p.Gln582Ter)	Likely pathogenic
3894573	NM_018161.5(NADSYN1):c.1036C>T (p.Arg346Ter)	Likely pathogenic
4845261	NM_018161.5(NADSYN1):c.475G>A (p.Gly159Arg)	Likely pathogenic
4849287	NM_018161.5(NADSYN1):c.317+2T>G	Likely pathogenic

SpliceAI

4153 predictions. Top by Δscore:

Variant	Effect	Δscore
11:71453380:GA:G	donor_gain	1.0000
11:71453382:G:GG	donor_gain	1.0000
11:71455104:TTACA:T	acceptor_loss	1.0000
11:71455105:TACA:T	acceptor_loss	1.0000
11:71455106:ACAGG:A	acceptor_loss	1.0000
11:71455107:CAGGT:C	acceptor_loss	1.0000
11:71455108:AGG:A	acceptor_loss	1.0000
11:71455109:G:GC	acceptor_loss	1.0000
11:71458541:GGAT:G	donor_gain	1.0000
11:71458542:GATG:G	donor_gain	1.0000
11:71472497:GCAG:G	donor_gain	1.0000
11:71472500:GGTG:G	donor_loss	1.0000
11:71472501:G:GA	donor_loss	1.0000
11:71472502:T:A	donor_loss	1.0000
11:71473269:C:CA	acceptor_gain	1.0000
11:71473273:T:A	acceptor_gain	1.0000
11:71473273:TGCA:T	acceptor_loss	1.0000
11:71473274:GCAG:G	acceptor_loss	1.0000
11:71473275:CAGGA:C	acceptor_loss	1.0000
11:71473276:A:AG	acceptor_gain	1.0000
11:71473276:AG:A	acceptor_gain	1.0000
11:71473277:G:GG	acceptor_gain	1.0000
11:71473277:GG:G	acceptor_gain	1.0000
11:71473277:GGA:G	acceptor_gain	1.0000
11:71473277:GGAA:G	acceptor_gain	1.0000
11:71473277:GGAAA:G	acceptor_gain	1.0000
11:71473330:G:GT	donor_gain	1.0000
11:71473362:CACAG:C	donor_loss	1.0000
11:71473363:ACAGG:A	donor_loss	1.0000
11:71473366:GG:G	donor_loss	1.0000

AlphaMissense

4659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:71453381:A:C	S29R	0.991
11:71455111:T:A	S29R	0.991
11:71455111:T:G	S29R	0.991
11:71464120:T:C	F129L	0.990
11:71464122:C:A	F129L	0.990
11:71464122:C:G	F129L	0.990
11:71455142:T:G	Y40D	0.988
11:71455147:G:C	R41S	0.987
11:71455147:G:T	R41S	0.987
11:71490879:A:C	S533R	0.985
11:71490881:T:A	S533R	0.985
11:71490881:T:G	S533R	0.985
11:71481959:A:C	S362R	0.983
11:71481961:C:A	S362R	0.983
11:71481961:C:G	S362R	0.983
11:71453362:T:A	N22K	0.982
11:71453362:T:G	N22K	0.982
11:71455146:G:C	R41T	0.981
11:71473601:A:T	E194V	0.978
11:71453318:G:C	A8P	0.977
11:71453351:T:C	F19L	0.977
11:71453353:C:A	F19L	0.977
11:71453353:C:G	F19L	0.977
11:71455167:T:A	I48K	0.977
11:71455146:G:T	R41M	0.976
11:71458444:G:C	D55H	0.976
11:71464121:T:C	F129S	0.976
11:71497533:G:C	R605S	0.973
11:71497533:G:T	R605S	0.973
11:71473604:T:A	I195N	0.972

dbSNP variants (sampled 300 via entrez): RS1000041704 (11:71489648 T>C), RS1000098507 (11:71455525 G>A), RS1000113089 (11:71460753 A>G), RS1000217776 (11:71494863 G>A), RS1000258593 (11:71491247 G>T), RS1000311508 (11:71465727 G>A,T), RS1000328982 (11:71465457 A>G), RS1000381962 (11:71499700 G>A,C), RS1000538440 (11:71493403 C>T), RS1000576538 (11:71472335 C>T), RS1000634177 (11:71498821 A>C,G), RS1000666838 (11:71498505 C>T), RS1000789932 (11:71466809 A>T), RS1000906855 (11:71470082 C>T), RS1000908282 (11:71493782 T>C)

Disease associations

OMIM: gene MIM:608285 | disease phenotypes: MIM:618845, MIM:617660

GenCC curated gene-disease

Disease	Classification	Inheritance
vertebral, cardiac, renal, and limb defects syndrome 3	Strong	Autosomal recessive
congenital vertebral-cardiac-renal anomalies syndrome	Supportive	Autosomal recessive

Mondo (3): vertebral, cardiac, renal, and limb defects syndrome 3 (MONDO:0030077), vertebral, cardiac, renal, and limb defects syndrome 1 (MONDO:0060554), congenital vertebral-cardiac-renal anomalies syndrome (MONDO:0020831)

Orphanet (0):

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000122	Unilateral renal agenesis
HP:0000960	Sacral dimple
HP:0001522	Death in infancy
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001719	Double outlet right ventricle
HP:0001762	Talipes equinovarus
HP:0002948	Vertebral fusion
HP:0003026	Short long bone
HP:0003422	Vertebral segmentation defect
HP:0004383	Hypoplastic left ventricle
HP:0005999	Ureteral atresia
HP:0010306	Short thorax
HP:0010958	Bilateral renal agenesis
HP:0011638	Anomalous origin of left coronary artery from the pulmonary artery

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000664_2	Vitamin D levels	3.000000e-09
GCST000697_1	Vitamin D insufficiency	2.000000e-27
GCST003155_13	Systemic lupus erythematosus	1.000000e-20
GCST005366_2	Vitamin D levels (dietary vitamin D intake interaction)	2.000000e-31
GCST005367_4	Vitamin D levels	4.000000e-62

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003762	vitamin D deficiency
EFO:0008539	vitamin D dietary intake measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
nicotinic acid adenine dinucleotide	affects cotreatment, increases activity, increases chemical synthesis	1
benzo(e)pyrene	decreases methylation	1
puag-haad	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Adenosine Triphosphate	affects cotreatment, increases activity, increases chemical synthesis	1
Ammonium Chloride	increases activity, increases chemical synthesis, affects cotreatment	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression, increases secretion	1
Doxorubicin	increases expression	1

Clinical trials (associated diseases)

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