NEGR1

Summary

NEGR1 (neuronal growth regulator 1, HGNC:17302) is a protein-coding gene on chromosome 1p31.1, encoding Neuronal growth regulator 1 (Q7Z3B1). May be involved in cell-adhesion.

Predicted to be involved in cell adhesion and regulation of synapse assembly. Predicted to act upstream of or within several processes, including cholesterol homeostasis; lipid droplet formation; and nervous system development. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in postsynaptic density.

Source: NCBI Gene 257194 — RefSeq curated summary.

At a glance

• GWAS associations: 159
• Clinical variants (ClinVar): 70 total — 1 likely-pathogenic
• MANE Select transcript: NM_173808

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17302
Approved symbol	NEGR1
Name	neuronal growth regulator 1
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	KILON, MGC46680, Ntra, IGLON4
Ensembl gene	ENSG00000172260
Ensembl biotype	protein_coding
OMIM	613173
Entrez	257194

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000306821, ENST00000357731, ENST00000467479, ENST00000474357, ENST00000478526

RefSeq mRNA: 1 — MANE Select: NM_173808 NM_173808

CCDS: CCDS661

Canonical transcript exons

ENST00000357731 — 7 exons

Exon	Start	End
ENSE00001176840	71592817	71592968
ENSE00001176848	71611026	71611146
ENSE00001176858	71698008	71698139
ENSE00001406972	72282319	72282539
ENSE00001453905	71395943	71407570
ENSE00003648526	71776172	71776297
ENSE00003692571	71935079	71935311

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 96.70.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1738 / max 401.9012, expressed in 874 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12831	6.3738	836
12829	0.4311	167
12830	0.1889	61
12832	0.1561	71
12826	0.0238	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 46	UBERON:0006483	96.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.65	gold quality
occipital lobe	UBERON:0002021	94.73	gold quality
primary visual cortex	UBERON:0002436	94.65	gold quality
superior frontal gyrus	UBERON:0002661	93.05	gold quality
dorsal root ganglion	UBERON:0000044	92.95	gold quality
superficial temporal artery	UBERON:0001614	92.57	gold quality
parietal lobe	UBERON:0001872	92.36	gold quality
middle temporal gyrus	UBERON:0002771	92.32	gold quality
calcaneal tendon	UBERON:0003701	92.24	gold quality
postcentral gyrus	UBERON:0002581	91.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.40	gold quality
prefrontal cortex	UBERON:0000451	91.34	gold quality
entorhinal cortex	UBERON:0002728	91.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.12	gold quality
endothelial cell	CL:0000115	90.97	gold quality
frontal cortex	UBERON:0001870	90.41	gold quality
neocortex	UBERON:0001950	89.73	gold quality
cerebral cortex	UBERON:0000956	89.41	gold quality
synovial joint	UBERON:0002217	88.91	gold quality
cauda epididymis	UBERON:0004360	88.69	gold quality
tibial nerve	UBERON:0001323	88.66	gold quality
cortical plate	UBERON:0005343	88.46	gold quality
superior vestibular nucleus	UBERON:0007227	88.09	gold quality
stromal cell of endometrium	CL:0002255	88.06	gold quality
temporal lobe	UBERON:0001871	87.83	gold quality
mucosa of stomach	UBERON:0001199	87.49	gold quality
skin of hip	UBERON:0001554	87.41	gold quality
medulla oblongata	UBERON:0001896	87.28	gold quality
layer of synovial tissue	UBERON:0007616	87.14	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	5075.95
E-GEOD-180759	yes	3715.84
E-MTAB-11268	yes	2217.18
E-CURD-119	yes	1796.65
E-GEOD-131882	yes	1541.10
E-HCAD-25	yes	79.98
E-HCAD-35	yes	67.91
E-ANND-3	yes	34.06
E-MTAB-6379	no	29.18
E-MTAB-7303	no	21.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

357 targeting NEGR1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467

Literature-anchored findings (GeneRIF, showing 30)

• Data suggest that in addition to its reported role in the brain, NEGR1 is also expressed in subcutaneous adipose tissue and acts as a central ‘hub’ in an obesity-related transcript network. (PMID:21427694)
• The results of these studies provide supporting evidence for MYEOV and NEGR1 as gene targets of 11q13 gains and 1p31 deletions in a neuroblastoma subset. (PMID:21624008)
• Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005 (PMID:21750520)
• Gene-treatment interactions were observed for long-term (NEGR1 rs2815752, Pmetformin*SNP = 0.028; FTO rs9939609, Plifestyle*SNP = 0.044) weight loss. (PMID:22179955)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Our study supports earlier reports of SH2B1 to be of importance in insulin sensitivity and, in addition, suggests potential roles of NEGR1 and MTCH2. (PMID:22443470)
• Results imply a regulatory role for TMEM18, BDNF, MTCH2 and NEGR1 in adipocyte differentiation and biology. In addition, we show a variation of MAF expression during adipogenesis, while NPC1, PTER and SH2B1 were not regulated. (PMID:23229156)
• Data indicate strong associations with severe obesity for single nucleotide polymorphism (SNP) rs9939609 within the FTO gene and SNP rs2815752 near the NEGR1 gene. (PMID:23950990)
• First study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity. (PMID:25072390)
• NEGR1 could be an important locus influencing certain personality dimensions in BN patients. (PMID:25245582)
• We observed novel selection signals in CDKAL1 and NEGR1, well-known diabetes and obesity susceptibility genes (PMID:25370040)
• Genetic variants associated with BMI and WHR in adults influence growth patterns and general and abdominal fat development from early childhood onwards. (PMID:25640768)
• Significant associations were identified at 3.5 years old for TMEM18 rs6548238, NEGR1 rs2815752, BDNF rs10767664 and rs6265 (1 year old and 3.5 years old) with anthropometric phenotypes (PMID:27005443)
• Single nucleotide polymorphism in NEGR1 gene is associated with major depressive disorder. (PMID:27479909)
• NEGR1 interacts with NPC2 and increases its protein stability; it has a role in obesity (PMID:27940359)
• Our results indicate a possible contribution of CNVs in LEPR, NEGR1, ARHGEF4, and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d to the development of obesity, particularly abdominal obesity in Mexican children. (PMID:28428959)
• NEGR1, strong candidate gene, associated with clinical features of Depression (e.g., earlier age at onset and recurrent and more severe forms of Depression). Gene expression patterns in the prefrontal and anterior cingulate cortex most closely matched the genetic findings. (PMID:28969442)
• Placental NEGR1 DNA methylation is associated with BMI and neurodevelopment in preschool-age children. (PMID:31510847)
• Integrating genome-wide association study and expression quantitative trait loci data identifies NEGR1 as a causal risk gene of major depression disorder. (PMID:32090785)
• 1p31.1 microdeletion including only NEGR1 gene in two patients. (PMID:32209393)
• analysis of genomic information from multiple non-cancer cohorts showed that both the NEGR1 promoter deletion and the BTNL3-8 deletion were CNVs occurring at high frequencies in the general population. Intriguingly, the upstream NEGR1 CNV deletion was homozygous in ~ 40% of individuals in the non-cancer population. (PMID:32375678)
• Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females. (PMID:32419576)
• Polymorphisms in Neuronal Growth Regulator 1 and Otoancorin Alternate the Susceptibility to Lung Cancer in Chinese Nonsmoking Females. (PMID:32552051)
• Highly Conserved Molecular Features in IgLONs Contrast Their Distinct Structural and Biological Outcomes. (PMID:32710982)
• Na/K-ATPase beta1-subunit associates with neuronal growth regulator 1 (NEGR1) to participate in intercellular interactions. (PMID:32958118)
• Depression in multiple sclerosis patients associated with risk variant near NEGR1. (PMID:33296963)
• CircDLGAP4 overexpression relieves oxygen-glucose deprivation-induced neuronal injury by elevating NEGR1 through sponging miR-503-3p. (PMID:34739656)
• Harnessing tissue-specific genetic variation to dissect putative causal pathways between body mass index and cardiometabolic phenotypes. (PMID:35090585)
• Plasma Neuronal Growth Regulator 1 May Link Physical Activity to Reduced Risk of Type 2 Diabetes: A Proteome-Wide Study of ARIC Participants. (PMID:37935012)
• The Association between Obesity Susceptibility and Polymorphisms of MC4R, SH2B1, and NEGR1 in Tibetans. (PMID:39034913)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	negr1	ENSDARG00000021607
mus_musculus	Negr1	ENSMUSG00000040037
rattus_norvegicus	Negr1	ENSRNOG00000021410
drosophila_melanogaster	Ama	FBGN0000071
drosophila_melanogaster	Lac	FBGN0010238
drosophila_melanogaster	klg	FBGN0017590
drosophila_melanogaster	fipi	FBGN0031627
drosophila_melanogaster	DIP-eta	FBGN0031725
drosophila_melanogaster	DIP-iota	FBGN0031837
drosophila_melanogaster	CG13506	FBGN0034723
drosophila_melanogaster	DIP-zeta	FBGN0051708
drosophila_melanogaster	DIP-kappa	FBGN0051814
drosophila_melanogaster	CG33543	FBGN0053543
drosophila_melanogaster	DIP-beta	FBGN0259245
drosophila_melanogaster	DIP-epsilon	FBGN0259714
caenorhabditis_elegans	rig-5	WBGENE00004372

Paralogs (5): IGLON5 (ENSG00000142549), NTM (ENSG00000182667), IGSF5 (ENSG00000183067), OPCML (ENSG00000183715), LSAMP (ENSG00000185565)

Protein

Protein identifiers

Neuronal growth regulator 1 — Q7Z3B1 (reviewed: Q7Z3B1)

Alternative names: IgLON family member 4

All UniProt accessions (1): Q7Z3B1

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cell-adhesion. May function as a trans-neural growth-promoting factor in regenerative axon sprouting in the mammalian brain.

Subcellular location. Cell membrane.

Similarity. Belongs to the immunoglobulin superfamily. IgLON family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z3B1-1	1	yes
Q7Z3B1-2	2

RefSeq proteins (1): NP_776169* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050876	IgLON_domain	Family

Pfam: PF07679, PF13927

UniProt features (48 total): strand 25, glycosylation site 6, disulfide bond 3, helix 3, domain 3, sequence conflict 2, signal peptide 1, chain 1, splice variant 1, propeptide 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6U6T	X-RAY DIFFRACTION	3.01
6DLD	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3B1-F1	81.98	0.67

Functional residue map

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

Post-translational modifications (2): 187, 324

Disulfide bonds (3): 60–118, 160–203, 245–297

Glycosylation sites (6): 275, 286, 294, 307, 73, 155

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 306 (showing top): GOBP_DIGESTION, E2F_Q4_01, HORIUCHI_WTAP_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, MYOGENIN_Q6, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_SYNAPSE_ASSEMBLY, GOBP_STEROL_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GCANCTGNY_MYOD_Q6, AAGCCAT_MIR135A_MIR135B, GOBP_NEUROGENESIS

GO Biological Process (21): brain development (GO:0007420), locomotory behavior (GO:0007626), feeding behavior (GO:0007631), protein secretion (GO:0009306), positive regulation of neuron projection development (GO:0010976), regulation of protein stability (GO:0031647), social behavior (GO:0035176), cholesterol homeostasis (GO:0042632), protein localization to plasma membrane raft (GO:0044860), fat cell differentiation (GO:0045444), positive regulation of saliva secretion (GO:0046878), neuron projection morphogenesis (GO:0048812), positive regulation of calcium-mediated signaling (GO:0050850), negative regulation of synapse assembly (GO:0051964), negative regulation of glial cell proliferation (GO:0060253), skeletal muscle organ development (GO:0060538), cell-cell adhesion (GO:0098609), lipid droplet formation (GO:0140042), cell adhesion (GO:0007155), neuron projection development (GO:0031175), regulation of synapse assembly (GO:0051963)

GO Molecular Function (2): transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), late endosome (GO:0005770), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), apical dendrite (GO:0097440), side of membrane (GO:0098552), membrane (GO:0016020), dendrite (GO:0030425)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
behavior	3
dendrite	3
neuron projection development	2
membrane	2
central nervous system development	1
animal organ development	1
head development	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
regulation of neuron projection development	1
positive regulation of cell projection organization	1
regulation of biological quality	1
biological process involved in intraspecies interaction between organisms	1
sterol homeostasis	1
protein localization to membrane raft	1
protein localization to cell periphery	1
cell differentiation	1
saliva secretion	1
regulation of saliva secretion	1
positive regulation of secretion	1
positive regulation of digestive system process	1
plasma membrane bounded cell projection morphogenesis	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
synapse assembly	1
negative regulation of nervous system development	1
regulation of synapse assembly	1
negative regulation of cell junction assembly	1
negative regulation of synapse organization	1
negative regulation of cell population proliferation	1
glial cell proliferation	1
negative regulation of gliogenesis	1
regulation of glial cell proliferation	1
muscle organ development	1
cell adhesion	1
lipid storage	1

Protein interactions and networks

STRING

1850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEGR1	KCTD15	Q96SI1	933
NEGR1	TMEM18	Q96B42	932
NEGR1	GNPDA2	Q8TDQ7	931
NEGR1	MTCH2	Q9Y6C9	893
NEGR1	SH2B1	Q9NRF2	887
NEGR1	FTO	Q9C0B1	850
NEGR1	MC4R	P32245	832
NEGR1	SEC16B	Q96JE7	768
NEGR1	FAIM2	Q9BWQ8	667
NEGR1	PCSK1	P29120	629
NEGR1	ETV5	P41161	601
NEGR1	NRXN3	Q9Y4C0	590
NEGR1	MC3R	P41968	583
NEGR1	BCDIN3D	Q7Z5W3	571
NEGR1	SDC3	O75056	569

IntAct

25 interactions, top by confidence:

A	B	Type	Score
NEGR1	NPC2	psi-mi:“MI:0915”(physical association)	0.640
NPC2	NEGR1	psi-mi:“MI:0915”(physical association)	0.640
NEGR1	NPC2	psi-mi:“MI:0403”(colocalization)	0.640
NEGR1	SYNGAP1	psi-mi:“MI:0915”(physical association)	0.500
NEGR1	LSAMP	psi-mi:“MI:0915”(physical association)	0.400
NEGR1	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
NEGR1	NTM	psi-mi:“MI:0915”(physical association)	0.400
NTM	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
NEGR1	GLMN	psi-mi:“MI:0915”(physical association)	0.400
BTN1A1	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
IGSF9B	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
OPCML	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
HTT	TPP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): NEGR1 (Affinity Capture-MS), NEGR1 (Affinity Capture-MS), NEGR1 (Affinity Capture-MS), GLMN (Affinity Capture-MS), NEGR1 (Affinity Capture-MS), NEGR1 (Proximity Label-MS), NEGR1 (Proximity Label-MS), NEGR1 (Proximity Label-MS), NEGR1 (Proximity Label-MS), NEGR1 (Proximity Label-MS), NEGR1 (Affinity Capture-MS), NEGR1 (Co-fractionation), PLOD1 (Co-fractionation), NEGR1 (Affinity Capture-RNA), NEGR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, A0JM41, A2VD98, B0CLX4, B6ZK77, D3YX43, F1LW30, O00241, O18906, O54901, O88775, O95256, P00545, P04218, P0C673, P10522, P13369, P17948, P21995, P27931, P35916, P35917, P35969, P37301, P42071, P42703, P53767, Q08DK1, Q15762, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5U2P2, Q5VJ70, Q6GMZ9, Q6PCB8, Q6X936, Q7TSN7

Diamond homologs: A5D7V5, Q2YHT5, Q2YHT7, Q5R412, Q5UKY4, Q6Q8B3, Q6XJV4, Q6XJV6, Q7Z3B1, Q80Z24, Q8BTP3, Q8TD46, Q9ES57, Q9ES58, Q9W6V2, Q9Z0J8, A2A8L5, A4IFW2, A6NGN9, A7MBJ4, B3N666, B4GBH0, B4GKZ8, B4HY03, B4KPU0, B4NZY8, B4Q599, P10586, P11834, P32736, Q03696, Q0E9H9, Q13449, Q14982, Q24372, Q26474, Q290N5, Q29JX6, Q58DA5, Q5IS61

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	49
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1298473	GRCh37/hg19 1p31.1(chr1:72400762-72400994)x1	Likely pathogenic

SpliceAI

4576 predictions. Top by Δscore:

Variant	Effect	Δscore
1:71407421:AAAAG:A	donor_gain	1.0000
1:71587341:A:AC	donor_gain	1.0000
1:71587342:C:CC	donor_gain	1.0000
1:71592811:ACT:A	donor_loss	1.0000
1:71592812:CT:C	donor_loss	1.0000
1:71592813:T:TC	donor_loss	1.0000
1:71592814:T:TG	donor_loss	1.0000
1:71592815:A:AC	donor_gain	1.0000
1:71592815:A:AT	donor_loss	1.0000
1:71592816:C:CA	donor_gain	1.0000
1:71592816:CG:C	donor_gain	1.0000
1:71592816:CGG:C	donor_gain	1.0000
1:71592816:CGGTT:C	donor_gain	1.0000
1:71611024:A:AC	donor_gain	1.0000
1:71611025:C:CC	donor_gain	1.0000
1:71611025:CTT:C	donor_gain	1.0000
1:71611027:T:TA	donor_gain	1.0000
1:71611034:T:A	donor_gain	1.0000
1:71698006:A:AC	donor_gain	1.0000
1:71698007:C:CC	donor_gain	1.0000
1:71698029:T:A	donor_gain	1.0000
1:71776167:TTTA:T	donor_loss	1.0000
1:71776169:TACCT:T	donor_loss	1.0000
1:71776170:A:AG	donor_loss	1.0000
1:71776171:C:A	donor_loss	1.0000
1:71776293:AGGAA:A	acceptor_gain	1.0000
1:71776294:GGAA:G	acceptor_gain	1.0000
1:71776295:GAA:G	acceptor_gain	1.0000
1:71776295:GAAC:G	acceptor_loss	1.0000
1:71776296:AA:A	acceptor_gain	1.0000

AlphaMissense

2307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:71592912:A:G	L282P	1.000
1:71611043:C:A	W257C	1.000
1:71611043:C:G	W257C	1.000
1:71611045:A:G	W257R	1.000
1:71611045:A:T	W257R	1.000
1:71776191:C:A	W172C	1.000
1:71776191:C:G	W172C	1.000
1:71592854:G:C	N301K	0.999
1:71592854:G:T	N301K	0.999
1:71592867:C:G	C297S	0.999
1:71592868:A:G	C297R	0.999
1:71592868:A:T	C297S	0.999
1:71611044:C:G	W257S	0.999
1:71611081:A:G	C245R	0.999
1:71698054:A:C	N207K	0.999
1:71698054:A:T	N207K	0.999
1:71698067:C:G	C203S	0.999
1:71698068:A:G	C203R	0.999
1:71698068:A:T	C203S	0.999
1:71698074:A:C	Y201D	0.999
1:71776192:C:G	W172S	0.999
1:71776193:A:G	W172R	0.999
1:71776193:A:T	W172R	0.999
1:71776229:A:G	C160R	0.999
1:71935142:A:C	Y116D	0.999
1:71935180:A:G	L103P	0.999
1:71935275:C:A	W71C	0.999
1:71935275:C:G	W71C	0.999
1:71592855:T:A	N301I	0.998
1:71592856:T:A	N301Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000001828 (1:71449678 T>A,C), RS1000007675 (1:72197572 T>C), RS1000008985 (1:71956209 C>T), RS1000011952 (1:71499617 T>A), RS1000014288 (1:71744603 T>C), RS1000016501 (1:72034520 C>T), RS1000017116 (1:72163428 G>A,C), RS1000019470 (1:71663949 G>A,T), RS1000023166 (1:72123375 T>C), RS1000023776 (1:71636932 G>A), RS1000024888 (1:71718074 T>C), RS1000025195 (1:71709307 C>G), RS1000027463 (1:71581123 G>T), RS1000029908 (1:71671111 C>G,T), RS1000033849 (1:71405811 A>G)

Disease associations

OMIM: gene MIM:613173 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

159 associations (top):

Study	Trait	p-value
GCST000080_16	Hemostatic factors and hematological phenotypes	2.000000e-06
GCST000144_3	Systemic lupus erythematosus	7.000000e-06
GCST000296_4	Body mass index	1.000000e-11
GCST000298_8	Body mass index	6.000000e-08
GCST000299_11	Weight	2.000000e-08
GCST000830_30	Body mass index	2.000000e-22
GCST001521_32	Subcutaneous adipose tissue	4.000000e-06
GCST001953_4	Obesity	1.000000e-13
GCST001953_51	Obesity	4.000000e-16
GCST001953_9	Obesity	2.000000e-17
GCST001955_4	Body mass index	2.000000e-14
GCST001957_3	Obesity (early onset extreme)	5.000000e-13
GCST001957_7	Obesity (early onset extreme)	2.000000e-08
GCST002021_13	Body mass index	1.000000e-06
GCST002541_28	Menarche (age at onset)	5.000000e-13
GCST002783_106	Body mass index	9.000000e-17
GCST002783_191	Body mass index	3.000000e-26
GCST002783_345	Body mass index	6.000000e-26
GCST002783_589	Body mass index	2.000000e-16
GCST002929_10	Chromium levels	5.000000e-06
GCST003177_23	Childhood body mass index	2.000000e-07
GCST004065_50	Waist circumference	2.000000e-10
GCST004065_56	Waist circumference	1.000000e-14
GCST004065_59	Waist circumference	1.000000e-07
GCST004066_101	Hip circumference	6.000000e-10
GCST004066_60	Hip circumference	4.000000e-11
GCST004271_1	Venlafaxine response in generalised anxiety disorder (HAMA-A score reduction after 24 weeks)	7.000000e-06
GCST004364_10	Intelligence	9.000000e-09
GCST004364_30	Intelligence	9.000000e-09
GCST004495_60	BMI (adjusted for smoking behaviour)	2.000000e-12

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0004703	age at menarche
EFO:0004337	intelligence
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004784	self reported educational attainment
EFO:0009180	rosacea severity measurement
EFO:0009185	heart rate response to recovery post exercise
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0009270	heel bone mineral density
EFO:0007041	obese body mass index status
EFO:1001870	late-onset Alzheimers disease
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0010130	health study participation
EFO:0009282	sodium measurement
EFO:0009695	household income
EFO:0008111	diet measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0005670	smoking initiation
EFO:0007800	body fat percentage
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
trichostatin A	increases expression	3
entinostat	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	affects methylation	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Panobinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression	1
Copper	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2DD	HAP1 NEGR1 (-) 1	Cancer cell line	Male
CVCL_E2DE	HAP1 NEGR1 (-) 2	Cancer cell line	Male
CVCL_E2DF	HAP1 NEGR1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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