GET4

Summary

GET4 (guided entry of tail-anchored proteins factor 4, HGNC:21690) is a protein-coding gene on chromosome 7p22.3, encoding Golgi to ER traffic protein 4 homolog (Q7L5D6). As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to…. It is a selective cancer dependency (DepMap: 24.2% of cell lines).

Enables protein carrier chaperone and protein-folding chaperone binding activity. Involved in establishment of protein localization to membrane; maintenance of unfolded protein; and proteolysis involved in protein catabolic process. Located in chromosome; cytosol; and nuclear lumen. Part of BAT3 complex. Implicated in congenital disorder of glycosylation type IIy.

Source: NCBI Gene 51608 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation, type IIy (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 90 total
• Phenotypes (HPO): 25
• Cancer dependency (DepMap): dependent in 24.2% of screened cell lines
• MANE Select transcript: NM_015949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21690
Approved symbol	GET4
Name	guided entry of tail-anchored proteins factor 4
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-20, H_NH1244M04.5, CEE, TRC35
Ensembl gene	ENSG00000239857
Ensembl biotype	protein_coding
OMIM	612056
Entrez	51608

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000265857, ENST00000407192, ENST00000412734, ENST00000426056, ENST00000441491, ENST00000464468, ENST00000483469, ENST00000881398, ENST00000919174, ENST00000919175, ENST00000919176, ENST00000954535, ENST00000954536

RefSeq mRNA: 1 — MANE Select: NM_015949 NM_015949

CCDS: CCDS5317

Canonical transcript exons

ENST00000265857 — 9 exons

Exon	Start	End
ENSE00001157244	876554	876800
ENSE00001557500	895334	896436
ENSE00003506038	892278	892418
ENSE00003523327	886056	886134
ENSE00003530149	893740	893815
ENSE00003544095	886569	886650
ENSE00003556615	893899	893971
ENSE00003786862	890928	891066
ENSE00003790445	887370	887519

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.7208 / max 462.5236, expressed in 1822 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76879	30.6160	1814
76878	9.6940	1755
76880	3.4521	1140
76877	0.5278	288
76884	0.4590	136
76888	0.3615	147
76881	0.3333	161
76883	0.1510	66
76882	0.1261	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.06	gold quality
right testis	UBERON:0004534	97.04	gold quality
pituitary gland	UBERON:0000007	96.26	gold quality
right adrenal gland cortex	UBERON:0035827	96.21	gold quality
left adrenal gland cortex	UBERON:0035825	96.10	gold quality
right uterine tube	UBERON:0001302	95.97	gold quality
adenohypophysis	UBERON:0002196	95.89	gold quality
lower esophagus mucosa	UBERON:0035834	95.83	gold quality
right adrenal gland	UBERON:0001233	95.77	gold quality
left adrenal gland	UBERON:0001234	95.75	gold quality
testis	UBERON:0000473	95.67	gold quality
right lobe of liver	UBERON:0001114	95.33	gold quality
metanephros cortex	UBERON:0010533	95.32	gold quality
adrenal gland	UBERON:0002369	94.81	gold quality
skin of leg	UBERON:0001511	94.50	gold quality
zone of skin	UBERON:0000014	94.22	gold quality
skin of abdomen	UBERON:0001416	94.17	gold quality
body of stomach	UBERON:0001161	94.10	gold quality
cortex of kidney	UBERON:0001225	94.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.85	gold quality
sural nerve	UBERON:0015488	93.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.79	gold quality
adult mammalian kidney	UBERON:0000082	93.64	gold quality
fundus of stomach	UBERON:0001160	93.51	gold quality
cerebellar hemisphere	UBERON:0002245	93.46	gold quality
body of pancreas	UBERON:0001150	93.43	gold quality
gastrocnemius	UBERON:0001388	93.39	gold quality
cerebellar cortex	UBERON:0002129	93.38	gold quality
cerebellum	UBERON:0002037	93.34	gold quality
esophagus mucosa	UBERON:0002469	93.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting GET4, 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-4481	100.00	66.42	1669
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-188-5P	97.89	67.01	756

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation. (PMID:23246001)
• Data indicate that the Bag6-Ubl4A-Trc35 complex is localized to the endoplasmic reticulum (ER) membrane to regulate ER-associated degradation (ERAD). (PMID:23665563)
• Data indicate that BCL2-associated athanogene 6 (BAG6) appears to be the central component for the process, as depletion of BAG6 leads to the loss of both UBL4A and GET4 proteins and resistance to cell killing by DNA-damaging agents. (PMID:23723067)
• The crystal structure of the Get3-Get4-Get5 complex in an ATP-bound state is presented. (PMID:24727835)
• Both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex. (PMID:25535373)
• GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein. (PMID:34704338)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	get4	ENSDARG00000024398
mus_musculus	Get4	ENSMUSG00000025858
drosophila_melanogaster	CG9853	FBGN0086605
caenorhabditis_elegans		WBGENE00017825

Protein

Protein identifiers

Golgi to ER traffic protein 4 homolog — Q7L5D6 (reviewed: Q7L5D6)

Alternative names: Conserved edge-expressed protein, Transmembrane domain recognition complex 35 kDa subunit

All UniProt accessions (4): Q7L5D6, C9JHN8, C9JPA8, C9JY46

UniProt curated annotations — full annotation on UniProt →

Function. As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome.

Subunit / interactions. Component of the BAG6/BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with BAG6; the interaction is direct and localizes BAG6 to the cytosol. Interacts with GET3.

Subcellular location. Cytoplasm. Cytosol.

Post-translational modifications. Ubiquitinated by RNF12, leading to proteasomal degradation. When unassembled from BAG6; ubiquitinylation is modulated by BAG6 quality control role and effectuated by RNF126.

Disease relevance. Congenital disorder of glycosylation 2Y (CDG2Y) [MIM:620200] A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2Y is an autosomal recessive form characterized by poor overall growth and global developmental delay with impaired intellectual development. Other features may include hypotonia, seizures, brain imaging abnormalities, dysmorphic features, and various skeletal defects. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the GET4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L5D6-1	1	yes
Q7L5D6-2	2

RefSeq proteins (1): NP_057033* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007317	GET4	Family
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily

Pfam: PF04190

UniProt features (44 total): helix 18, mutagenesis site 14, region of interest 2, sequence conflict 2, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, strand 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6AU8	X-RAY DIFFRACTION	1.8
7RU9	ELECTRON MICROSCOPY	3.3
7RUA	ELECTRON MICROSCOPY	3.4
7RUC	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L5D6-F1	88.53	0.79

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): 2, 12

Mutagenesis-validated functional residues (14):

Position	Phenotype
29	loss of interaction with get3; when associated with d-25. impairs tail-anchored protein delivery; when associetd with d-
84	reduces tail-anchored protein delivery.
182	no effect on interaction with bag6.
188	no effect on interaction with bag6.
195	no effect on interaction with bag6.
241	no effect on interaction with bag6.
242	no effect on interaction with bag6.
257	no effect on interaction with bag6.
258	no effect on interaction with bag6.
259	no effect on interaction with bag6.
262	inhibits interaction with bag6.
266	no effect on interaction with bag6.
278	no effect on interaction with get3. no effect on tail-anchored protein delivery.
25	loss of interaction with get3; when associated with d-29. impairs tail-anchored protein delivery; when associetd with d-

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane

MSigDB gene sets: 169 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, chr7p22, FOXD3_01, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, HP1SITEFACTOR_Q6, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION

GO Biological Process (7): ubiquitin-dependent protein catabolic process (GO:0006511), post-translational protein targeting to endoplasmic reticulum membrane (GO:0006620), regulation of protein stability (GO:0031647), ERAD pathway (GO:0036503), obsolete maintenance of unfolded protein (GO:0036506), protein insertion into ER membrane (GO:0045048), tail-anchored membrane protein insertion into ER membrane (GO:0071816)

GO Molecular Function (3): protein-folding chaperone binding (GO:0051087), protein carrier activity (GO:0140597), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), BAT3 complex (GO:0071818)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
intracellular membraneless organelle	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein targeting to membrane	1
protein targeting to ER	1
regulation of biological quality	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
endoplasmic reticulum organization	1
protein localization to organelle	1
protein insertion into membrane	1
protein insertion into ER membrane	1
protein binding	1
molecular carrier activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
ER membrane insertion complex	1

Protein interactions and networks

STRING

971 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GET4	UBL4A	P11441	999
GET4	GET3	O43681	997
GET4	SGTA	O43765	994
GET4	BAG6	P46379	990
GET4	GET1	O00258	914
GET4	CAMLG	P49069	784
GET4	BAG1	Q99933	734
GET4	RNF126	Q9BV68	640
GET4	AMFR	P26442	599
GET4	SRP54	P13624	583
GET4	SGTB	Q96EQ0	536
GET4	STX5	Q13190	516
GET4	PRRC2A	P48634	513
GET4	SEC61A1	P38378	495
GET4	TMEM208	Q9BTX3	490

IntAct

162 interactions, top by confidence:

A	B	Type	Score
GET4	PRKAB2	psi-mi:“MI:0915”(physical association)	0.830
PRKAB2	GET4	psi-mi:“MI:0915”(physical association)	0.830
GET3	GET4	psi-mi:“MI:0915”(physical association)	0.800
GET4	GET3	psi-mi:“MI:0914”(association)	0.800
GET4	UBL4A	psi-mi:“MI:0914”(association)	0.730
NPRL2	DEPDC5	psi-mi:“MI:0914”(association)	0.730
BAG6	GET4	psi-mi:“MI:0915”(physical association)	0.670
SGTB	SGTA	psi-mi:“MI:0914”(association)	0.670
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
GET4	DUSP21	psi-mi:“MI:0915”(physical association)	0.560
FBN1	GET4	psi-mi:“MI:0915”(physical association)	0.560
GET4	NUP85	psi-mi:“MI:0915”(physical association)	0.560
GET4	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
GET4	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
GIT2	GET4	psi-mi:“MI:0915”(physical association)	0.560
GET4	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	GET4	psi-mi:“MI:0915”(physical association)	0.560
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
KCNA6	KCNA3	psi-mi:“MI:0914”(association)	0.530
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
KLHL10	PXDNL	psi-mi:“MI:0914”(association)	0.530
MYEOV	BAG6	psi-mi:“MI:0914”(association)	0.530

BioGRID (229): GET4 (Affinity Capture-MS), GET4 (Two-hybrid), GET4 (Affinity Capture-RNA), GET4 (Affinity Capture-Western), GET4 (Affinity Capture-Western), BAG6 (Two-hybrid), GET4 (Affinity Capture-MS), UBL4A (Affinity Capture-MS), BAG6 (Affinity Capture-MS), ASNA1 (Affinity Capture-MS), GET4 (Affinity Capture-MS), GET4 (Affinity Capture-MS), GET4 (Affinity Capture-MS), GET4 (Affinity Capture-MS), GET4 (Affinity Capture-MS)

ESM2 similar proteins: A0MT11, A1Z3X3, A2VD00, A4GWN3, A4II09, A4QNE0, A4VCH4, B5KFI0, O35841, P23116, P49754, Q09161, Q0P5I8, Q14152, Q15006, Q15386, Q1JU68, Q3B8M3, Q5E993, Q5E9L7, Q5KU39, Q5R4J9, Q5R644, Q5R882, Q5RE70, Q5XI83, Q5ZJZ6, Q5ZKG8, Q5ZMW3, Q68E01, Q6GLK9, Q6N069, Q6NRL4, Q6PCR7, Q6TGY8, Q6WKZ8, Q7L5D6, Q7TPD0, Q80UM3, Q8BHL5

Diamond homologs: A0MT11, A1Z3X3, A4GWN3, A4QNE0, B5KFI0, Q0P5I8, Q54TH4, Q5ZKG8, Q6GLK9, Q6NRL4, Q7L5D6, Q9D1H7, Q9VN19, Q6GKV1, O74432, Q4WDK4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	5	22.9×	2e-04
AUF1 (hnRNP D0) binds and destabilizes mRNA	7	16.7×	6e-05
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	8	14.9×	4e-05
Defective CFTR causes cystic fibrosis	7	14.8×	7e-05
Negative regulation of NOTCH4 signaling	6	13.7×	4e-04
Regulation of activated PAK-2p34 by proteasome mediated degradation	5	13.4×	2e-03
Vpu mediated degradation of CD4	5	12.8×	2e-03
Autodegradation of the E3 ubiquitin ligase COP1	5	12.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	14	5.1×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1880 predictions. Top by Δscore:

Variant	Effect	Δscore
7:876797:TCAG:T	donor_loss	1.0000
7:876798:CAGGT:C	donor_loss	1.0000
7:876800:GG:G	donor_loss	1.0000
7:876801:G:GC	donor_loss	1.0000
7:876802:T:A	donor_loss	1.0000
7:886050:T:TA	acceptor_gain	1.0000
7:886051:GGCA:G	acceptor_loss	1.0000
7:886052:GCA:G	acceptor_loss	1.0000
7:886053:CA:C	acceptor_loss	1.0000
7:886054:A:AT	acceptor_loss	1.0000
7:886055:G:A	acceptor_loss	1.0000
7:886055:GGTAC:G	acceptor_gain	1.0000
7:886130:GCCAG:G	donor_gain	1.0000
7:886134:GGTAA:G	donor_loss	1.0000
7:886135:G:GG	donor_gain	1.0000
7:886136:T:G	donor_loss	1.0000
7:886565:GTAGC:G	acceptor_loss	1.0000
7:886566:TA:T	acceptor_loss	1.0000
7:886567:A:AC	acceptor_loss	1.0000
7:886567:A:AG	acceptor_gain	1.0000
7:886568:G:A	acceptor_loss	1.0000
7:886568:G:GA	acceptor_gain	1.0000
7:886568:GC:G	acceptor_gain	1.0000
7:886568:GCA:G	acceptor_gain	1.0000
7:886568:GCAA:G	acceptor_gain	1.0000
7:886568:GCAAA:G	acceptor_gain	1.0000
7:886646:GCTGG:G	donor_gain	1.0000
7:886649:GG:G	donor_gain	1.0000
7:886650:GG:G	donor_gain	1.0000
7:887368:A:AG	acceptor_gain	1.0000

AlphaMissense

2137 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:876718:C:T	R25C	1.000
7:876734:T:C	L30P	1.000
7:876763:T:C	Y40H	1.000
7:876769:G:C	A42P	1.000
7:876772:C:G	H43D	1.000
7:876777:G:C	Q44H	1.000
7:876777:G:T	Q44H	1.000
7:876781:T:G	Y46D	1.000
7:876785:G:C	R47P	1.000
7:876791:T:C	L49P	1.000
7:876799:A:G	R52G	1.000
7:876800:G:C	R52T	1.000
7:876800:G:T	R52M	1.000
7:886056:G:C	R52S	1.000
7:886056:G:T	R52S	1.000
7:886106:G:A	G69E	1.000
7:886588:T:G	L85W	1.000
7:892400:T:C	L243P	1.000
7:876718:C:A	R25S	0.999
7:876730:A:G	K29E	0.999
7:876734:T:A	L30Q	0.999
7:876746:T:A	V34D	0.999
7:876764:A:G	Y40C	0.999
7:876770:C:A	A42E	0.999
7:876776:A:C	Q44P	0.999
7:876779:T:C	M45T	0.999
7:876784:C:G	R47G	0.999
7:876796:T:C	F51L	0.999
7:876798:C:A	F51L	0.999
7:876798:C:G	F51L	0.999

dbSNP variants (sampled 300 via entrez): RS1000164185 (7:895898 C>T), RS1000288672 (7:876243 C>A,G), RS1000322171 (7:886836 C>T), RS1000400193 (7:880982 A>G), RS1000416128 (7:877869 T>A,C), RS1000468610 (7:877449 A>C,G), RS1000533959 (7:885787 C>G,T), RS1000551998 (7:884455 A>G), RS1000812543 (7:892786 CGT>C), RS1000812705 (7:882408 A>C), RS1000815660 (7:891697 G>A), RS1001053139 (7:889159 C>G,T), RS1001110897 (7:887811 C>T), RS1001182784 (7:882562 G>A), RS1001216461 (7:887255 C>T)

Disease associations

OMIM: gene MIM:612056 | disease phenotypes: MIM:620200

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of glycosylation, type IIy	Limited	Autosomal recessive

Mondo (1): congenital disorder of glycosylation, type IIy (MONDO:0859356)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000341	Narrow forehead
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001344	Absent speech
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002133	Status epilepticus
HP:0002188	Delayed CNS myelination
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0003593	Infantile onset
HP:0004349	Reduced bone mineral density
HP:0004395	Malnutrition
HP:0007141	Sensorimotor neuropathy
HP:0007366	Atrophy/Degeneration affecting the brainstem
HP:0012301	Type II transferrin isoform profile
HP:0025336	Delayed ability to sit
HP:0030043	Hip subluxation
HP:0031936	Delayed ability to walk
HP:0033725	Thin corpus callosum

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010320_83	PR interval	2.000000e-09
GCST010321_28	PR interval	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
tetrabromobisphenol A	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
bisphenol AF	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Arsenicals	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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