ERLEC1

Summary

ERLEC1 (endoplasmic reticulum lectin 1, HGNC:25222) is a protein-coding gene on chromosome 2p16.2, encoding Endoplasmic reticulum lectin 1 (Q96DZ1). Probable lectin that binds selectively to improperly folded lumenal proteins.

This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21.

Source: NCBI Gene 27248 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant prognathism (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 100 total — 4 likely-pathogenic
• MANE Select transcript: NM_015701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25222
Approved symbol	ERLEC1
Name	endoplasmic reticulum lectin 1
Location	2p16.2
Locus type	gene with protein product
Status	Approved
Aliases	CL25084, XTP3TPB, XTP3-B, ERLECTIN
Ensembl gene	ENSG00000068912
Ensembl biotype	protein_coding
OMIM	611229
Entrez	27248

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 32 protein_coding, 14 retained_intron, 10 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000185150, ENST00000378239, ENST00000405123, ENST00000494373, ENST00000684835, ENST00000684875, ENST00000685400, ENST00000685508, ENST00000686424, ENST00000687536, ENST00000687552, ENST00000687712, ENST00000687723, ENST00000688096, ENST00000688147, ENST00000688274, ENST00000688464, ENST00000689100, ENST00000689106, ENST00000689230, ENST00000689291, ENST00000689496, ENST00000689887, ENST00000689943, ENST00000690020, ENST00000690280, ENST00000690740, ENST00000690769, ENST00000690836, ENST00000691065, ENST00000691171, ENST00000691217, ENST00000691853, ENST00000691939, ENST00000692267, ENST00000692350, ENST00000692516, ENST00000692665, ENST00000692745, ENST00000692786, ENST00000692971, ENST00000693288, ENST00000693696, ENST00000901753, ENST00000901754, ENST00000901755, ENST00000901756, ENST00000901757, ENST00000901758, ENST00000913946, ENST00000913947, ENST00000913948, ENST00000952238, ENST00000952239, ENST00000952240, ENST00000952241, ENST00000952242

RefSeq mRNA: 3 — MANE Select: NM_015701 NM_001127397, NM_001127398, NM_015701

CCDS: CCDS1848, CCDS46283, CCDS46284

Canonical transcript exons

ENST00000185150 — 14 exons

Exon	Start	End
ENSE00000480955	53812949	53813073
ENSE00000752647	53794345	53794449
ENSE00000752711	53795933	53796013
ENSE00000752751	53797515	53797592
ENSE00000752787	53797732	53797795
ENSE00000752788	53801397	53801620
ENSE00000752789	53801713	53801842
ENSE00000752790	53808299	53808460
ENSE00000752791	53809214	53809273
ENSE00000752792	53814543	53814620
ENSE00000752793	53814860	53814935
ENSE00000995995	53799047	53799081
ENSE00003841937	53817898	53818796
ENSE00003847081	53787044	53787372

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.7815 / max 504.0265, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20234	46.7554	1823
20235	4.7495	1409
20233	2.2381	1235
20236	0.9429	467
20232	0.0956	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	99.34	gold quality
endothelial cell	CL:0000115	98.58	gold quality
ileal mucosa	UBERON:0000331	98.26	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.25	gold quality
oviduct epithelium	UBERON:0004804	98.14	gold quality
tibia	UBERON:0000979	98.12	gold quality
tibialis anterior	UBERON:0001385	98.06	gold quality
pancreatic ductal cell	CL:0002079	97.80	gold quality
decidua	UBERON:0002450	97.76	gold quality
corpus epididymis	UBERON:0004359	97.70	gold quality
middle temporal gyrus	UBERON:0002771	97.69	gold quality
left ventricle myocardium	UBERON:0006566	97.67	gold quality
nasal cavity epithelium	UBERON:0005384	97.55	gold quality
islet of Langerhans	UBERON:0000006	97.41	gold quality
parotid gland	UBERON:0001831	97.38	gold quality
seminal vesicle	UBERON:0000998	97.37	gold quality
oocyte	CL:0000023	97.25	gold quality
saphenous vein	UBERON:0007318	97.17	gold quality
bronchial epithelial cell	CL:0002328	96.90	gold quality
palpebral conjunctiva	UBERON:0001812	96.87	gold quality
bronchus	UBERON:0002185	96.87	gold quality
placenta	UBERON:0001987	96.78	gold quality
myocardium	UBERON:0002349	96.72	gold quality
eye	UBERON:0000970	96.71	gold quality
caput epididymis	UBERON:0004358	96.52	gold quality
pancreas	UBERON:0001264	96.48	gold quality
superficial temporal artery	UBERON:0001614	96.47	gold quality
visceral pleura	UBERON:0002401	96.37	gold quality
deltoid	UBERON:0001476	96.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.32	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	52.52
E-HCAD-1	yes	48.03
E-MTAB-9467	yes	47.96
E-HCAD-4	yes	46.18
E-CURD-46	yes	33.30
E-MTAB-8410	yes	29.11
E-HCAD-9	yes	14.89
E-MTAB-10553	yes	9.77
E-MTAB-4850	no	1390.61
E-HCAD-32	no	676.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting ERLEC1, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5580-3P	99.70	69.41	2052

Literature-anchored findings (GeneRIF, showing 10)

• Erlectin functions in N-glycan recognition in the endoplasmic reticulum and may regulate glycoprotein traffic (PMID:16531414)
• XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP (PMID:18502753)
• XTP3-B specifically binds to AT(NHK), which is a well-known substrate of ERAD, via a C-terminal MRH domain in a glycan-dependent manner. (PMID:19917667)
• mannose trimming enables delivery of a substrate glycoprotein from EDEM1 to late endoplsmic reticulum degredation steps through association with XTP3-B (PMID:21062743)
• Findings shed light on how tolerance to multiple cellular stresses at a metastatic site can be evoked by an integrated mechanism involving CIM, ERLEC1, which can function to coordinate those responses in a manner that promotes metastatic cell survival. (PMID:21118962)
• It regulates endoplasmic reticulum-associated degradation. (review) (PMID:21404621)
• Data indicate that the interaction of OS-9 and XTP3-B with CD147(CG) was inhibited by mutations to conserved residues in their lectin domains. (PMID:23097496)
• Lectin activity of XTP3-B is required for its interaction with the misfolded glycoprotein alpha1-antitrypsin variant. (PMID:23356641)
• The relative expression of OS9 and XTP3B and the distribution of glycan and non-glycan degrons within the same protein contribute to the fidelity. (PMID:29706535)
• Identification of pathogenic variants of ERLEC1 in individuals with Class III malocclusion by exome sequencing. (PMID:32442352)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	erlec1	ENSDARG00000086309
mus_musculus	Erlec1	ENSMUSG00000020311
rattus_norvegicus	Erlec1	ENSRNOG00000007283
drosophila_melanogaster	CG6766	FBGN0032398
caenorhabditis_elegans	Y105E8A.2	WBGENE00013667

Paralogs (1): OS9 (ENSG00000135506)

Protein

Protein identifiers

Endoplasmic reticulum lectin 1 — Q96DZ1 (reviewed: Q96DZ1)

Alternative names: ER lectin, XTP3-transactivated gene B protein

All UniProt accessions (25): Q96DZ1, A0A8I5KQC1, A0A8I5KR40, A0A8I5KRL2, A0A8I5KS40, A0A8I5KSC7, A0A8I5KTC7, A0A8I5KTD9, A0A8I5KTW2, A0A8I5KU16, A0A8I5KU57, A0A8I5KUG7, A0A8I5KUW0, A0A8I5KV23, A0A8I5KVG1, A0A8I5KVT1, A0A8I5KWA3, A0A8I5KWJ1, A0A8I5KXM1, A0A8I5KXV7, A0A8I5KXY6, A0A8I5KY03, A0A8I5KYU6, A0A8I5KYX4, V9HWD3

UniProt curated annotations — full annotation on UniProt →

Function. Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins.

Subunit / interactions. May form a complex with OS9, HSPA5, SYVN1, and SEL1L with which it interacts directly. Interacts (via PRKCSH 2 domain) with KREMEN2 (when glycosylated). Interacts with HSPA5.

Subcellular location. Endoplasmic reticulum lumen.

Post-translational modifications. Isoform 1 and isoform 2 are N-glycosylated.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96DZ1-1	1, hXTP3B-long	yes
Q96DZ1-2	2, hXTP3B-short
Q96DZ1-3	3

RefSeq proteins (3): NP_001120869, NP_001120870, NP_056516* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009011	Man6P_isomerase_rcpt-bd_dom_sf	Homologous_superfamily
IPR012913	OS9-like_dom	Domain
IPR044865	MRH_dom	Domain
IPR045149	OS-9-like	Family

Pfam: PF07915

UniProt features (42 total): strand 18, disulfide bond 6, mutagenesis site 3, helix 3, splice variant 2, sequence conflict 2, domain 2, turn 2, signal peptide 1, chain 1, sequence variant 1, glycosylation site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8KET	ELECTRON MICROSCOPY	3.3
8KES	ELECTRON MICROSCOPY	3.5
8KEV	ELECTRON MICROSCOPY	3.5
9LWU	ELECTRON MICROSCOPY	3.5
9UAV	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DZ1-F1	73.86	0.26

Functional residue map

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

Disulfide bonds (6): 436–467, 113–126, 199–232, 215–244, 344–357, 421–455

Glycosylation sites (1): 195

Mutagenesis-validated functional residues (3):

Position	Phenotype
207	abolishes interaction with sel1l.
379	abolishes binding to kremen2.
428	abolishes interaction with sel1l.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-5358346	Hedgehog ligand biogenesis
R-HSA-5362768	Hh mutants are degraded by ERAD
R-HSA-5678895	Defective CFTR causes cystic fibrosis
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)

MSigDB gene sets: 148 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, HIF1_Q3

GO Biological Process (4): endoplasmic reticulum unfolded protein response (GO:0030968), retrograde protein transport, ER to cytosol (GO:0030970), ERAD pathway (GO:0036503), negative regulation of retrograde protein transport, ER to cytosol (GO:1904153)

GO Molecular Function (3): obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (3): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum quality control compartment (GO:0044322), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Transport of small molecules	1
Signaling by Hedgehog	1
Hh mutants abrogate ligand secretion	1
ABC transporter disorders	1
Regulation of PD-L1(CD274) Post-translational modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	2
binding	2
endoplasmic reticulum	2
cellular response to unfolded protein	1
intracellular signal transduction	1
protein exit from endoplasmic reticulum	1
ERAD pathway	1
endoplasmic reticulum to cytosol transport	1
proteasomal protein catabolic process	1
response to chemical	1
retrograde protein transport, ER to cytosol	1
negative regulation of protein exit from endoplasmic reticulum	1
regulation of retrograde protein transport, ER to cytosol	1
intracellular organelle lumen	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1275 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERLEC1	SEL1L	Q9UBV2	949
ERLEC1	CANX	P27824	942
ERLEC1	KREMEN2	Q8NCW0	916
ERLEC1	EDEM1	Q92611	886
ERLEC1	HSP90B1	P14625	881
ERLEC1	MAN1B1	Q9UKM7	876
ERLEC1	DERL2	Q9GZP9	812
ERLEC1	DERL1	Q9BUN8	809
ERLEC1	UBE2G2	P56554	804
ERLEC1	FAM8A1	Q9UBU6	798
ERLEC1	SYVN1	Q86TM6	795
ERLEC1	UBE2J1	Q9Y385	792
ERLEC1	UGGT1	Q9NYU2	781
ERLEC1	FAF2	Q96CS3	756
ERLEC1	AMFR	P26442	751

IntAct

99 interactions, top by confidence:

A	B	Type	Score
SEL1L	OS9	psi-mi:“MI:0914”(association)	0.860
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
CHST8	CANX	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
ERLEC1	ATF6	psi-mi:“MI:0914”(association)	0.530
	PLOD2	psi-mi:“MI:0914”(association)	0.530
ERLEC1	SEL1L	psi-mi:“MI:0914”(association)	0.530
LIPG	NRP1	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
SMPD1	CLGN	psi-mi:“MI:0914”(association)	0.530
GAA	CLGN	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
env	FLOT1	psi-mi:“MI:0914”(association)	0.460
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
ERLEC1	STK11	psi-mi:“MI:0915”(physical association)	0.370
Ncstn	DERL1	psi-mi:“MI:0914”(association)	0.350
Sel1l	HSP90B1	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
K8.1	EXOC5	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350

BioGRID (239): SLC27A3 (Affinity Capture-MS), SYVN1 (Affinity Capture-MS), OS9 (Affinity Capture-MS), UBE2G2 (Affinity Capture-MS), DERL2 (Affinity Capture-MS), UBE2J1 (Affinity Capture-MS), SEL1L (Affinity Capture-MS), CPVL (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), SYVN1 (Affinity Capture-Western), UBE2J1 (Affinity Capture-Western)

ESM2 similar proteins: A2ATD1, A8WCC4, B1AKI9, O19011, O35757, O73753, O75129, O95980, P01137, P03970, P04202, P07200, P07995, P08476, P09533, P09858, P17246, P17247, P18331, P18341, P27092, P27424, P31515, P43032, P49767, P50414, P54831, P55001, P55002, P55102, P97953, Q04998, Q07257, Q38HS2, Q5R8S4, Q5RA73, Q6DF53, Q6X2S4, Q80Z10, Q8CI19

Diamond homologs: Q08B78, Q28IT1, Q5R8S4, Q67WM9, Q8GWH3, Q8VEH8, Q96DZ1, Q13438, Q3MHX6, Q4IEA7, Q4WCG2, Q5BDB9, Q5RKH6, Q6CNH1, Q8K2C7, Q872S3, Q5ACR4, Q6BJ08, Q6FV52, Q99220, Q9UTC8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Hedgehog ligand biogenesis	6	14.1×	7e-04
Hh mutants are degraded by ERAD	5	13.5×	3e-03
Defective CFTR causes cystic fibrosis	5	12.2×	4e-03
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	10.8×	5e-03
R-HSA-425393	6	8.7×	4e-03
SLC-mediated transmembrane transport	12	7.9×	2e-05
Transport of small molecules	16	4.5×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
retrograde protein transport, ER to cytosol	5	44.6×	3e-05
ERAD pathway	12	19.6×	8e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	66
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
830376	NM_015701.5(ERLEC1):c.1237C>T (p.His413Tyr)	Likely pathogenic
830377	NM_015701.5(ERLEC1):c.419C>G (p.Thr140Ser)	Likely pathogenic
830378	NM_015701.5(ERLEC1):c.419C>T (p.Thr140Ile)	Likely pathogenic
830379	NM_015701.5(ERLEC1):c.1448A>G (p.Asn483Ser)	Likely pathogenic

SpliceAI

2050 predictions. Top by Δscore:

Variant	Effect	Δscore
2:53794337:A:AG	acceptor_gain	1.0000
2:53794338:T:G	acceptor_gain	1.0000
2:53794340:T:TA	acceptor_gain	1.0000
2:53794342:CA:C	acceptor_loss	1.0000
2:53794343:A:AG	acceptor_gain	1.0000
2:53794344:G:A	acceptor_loss	1.0000
2:53794344:G:GA	acceptor_gain	1.0000
2:53794344:GC:G	acceptor_gain	1.0000
2:53794344:GCC:G	acceptor_gain	1.0000
2:53794344:GCCC:G	acceptor_gain	1.0000
2:53794344:GCCCA:G	acceptor_gain	1.0000
2:53794445:ATGAG:A	donor_gain	1.0000
2:53794446:TGAG:T	donor_gain	1.0000
2:53794447:GAG:G	donor_gain	1.0000
2:53794447:GAGG:G	donor_gain	1.0000
2:53794448:AG:A	donor_gain	1.0000
2:53794448:AGGT:A	donor_loss	1.0000
2:53794449:GG:G	donor_gain	1.0000
2:53794449:GGTA:G	donor_loss	1.0000
2:53794450:G:GG	donor_gain	1.0000
2:53796012:GA:G	donor_gain	1.0000
2:53796014:G:GG	donor_gain	1.0000
2:53797509:TTTTA:T	acceptor_loss	1.0000
2:53797510:TTTAG:T	acceptor_loss	1.0000
2:53797512:TAGAT:T	acceptor_loss	1.0000
2:53797513:A:AG	acceptor_gain	1.0000
2:53797513:A:C	acceptor_loss	1.0000
2:53797513:AGATT:A	acceptor_gain	1.0000
2:53797514:G:GT	acceptor_gain	1.0000
2:53797514:GA:G	acceptor_gain	1.0000

AlphaMissense

3170 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:53787351:G:C	W47C	1.000
2:53787351:G:T	W47C	1.000
2:53794417:T:A	C79S	1.000
2:53794417:T:C	C79R	1.000
2:53794418:G:C	C79S	1.000
2:53797529:G:C	W121C	1.000
2:53797529:G:T	W121C	1.000
2:53801466:T:A	C199S	1.000
2:53801466:T:C	C199R	1.000
2:53801467:G:A	C199Y	1.000
2:53801467:G:C	C199S	1.000
2:53801468:T:G	C199W	1.000
2:53801514:T:A	C215S	1.000
2:53801514:T:C	C215R	1.000
2:53801515:G:A	C215Y	1.000
2:53801515:G:C	C215S	1.000
2:53801516:T:G	C215W	1.000
2:53801565:T:A	C232S	1.000
2:53801565:T:C	C232R	1.000
2:53801566:G:A	C232Y	1.000
2:53801566:G:C	C232S	1.000
2:53801566:G:T	C232F	1.000
2:53801567:T:G	C232W	1.000
2:53801744:T:A	C261S	1.000
2:53801744:T:C	C261R	1.000
2:53801745:G:A	C261Y	1.000
2:53801745:G:C	C261S	1.000
2:53809225:G:C	W351C	1.000
2:53809225:G:T	W351C	1.000
2:53809226:T:A	W352R	1.000

dbSNP variants (sampled 300 via entrez): RS1000099869 (2:53786569 GA>G), RS1000112702 (2:53804703 A>G), RS1000265376 (2:53789042 C>A), RS1000511447 (2:53801806 A>G), RS1000539614 (2:53810861 C>G), RS1000624502 (2:53789177 T>C,G), RS1001030662 (2:53793756 T>G), RS1001040513 (2:53793496 A>C,G), RS1001051180 (2:53787652 G>A), RS1001194326 (2:53795840 A>G), RS1001270259 (2:53790243 G>A), RS1001280948 (2:53798963 A>C,G), RS1001285874 (2:53785242 C>A), RS1001313491 (2:53786859 G>T), RS1001414517 (2:53814075 C>G)

Disease associations

OMIM: gene MIM:611229 | disease phenotypes: MIM:176700

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant prognathism	Strong	Autosomal dominant

Mondo (1): autosomal dominant prognathism (MONDO:0008312)

Orphanet (1): Autosomal dominant prognathism (Orphanet:2964)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST006193_90	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-11
GCST006194_1	Diastolic blood pressure x smoking status (current vs non-current) interaction (1df test)	2.000000e-09
GCST006585_2991	Blood protein levels	2.000000e-07
GCST010002_365	Refractive error	3.000000e-34
GCST90002385_129	High light scatter reticulocyte count	2.000000e-16
GCST90002386_246	High light scatter reticulocyte percentage of red cells	3.000000e-15
GCST90002405_124	Reticulocyte count	2.000000e-18
GCST90002406_16	Reticulocyte fraction of red cells	5.000000e-17

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008313	Malocclusion, Angle Class III	C07.793.494.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
bisphenol A	affects expression, decreases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
aristolochic acid I	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Curcumin	increases expression	1
Hydralazine	increases expression, affects cotreatment	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tunicamycin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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