CAMLG

Summary

CAMLG (calcium modulating ligand, HGNC:1471) is a protein-coding gene on chromosome 5q31.1, encoding Guided entry of tail-anchored proteins factor CAMLG (P49069). Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. It is a selective cancer dependency (DepMap: 40.2% of cell lines).

The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin B, cyclosporin A binds and inactivates the key signaling intermediate calcineurin. The protein encoded by this gene functions similarly to cyclosporin A, binding to cyclophilin B and acting downstream of the TCR and upstream of calcineurin by causing an influx of calcium. This integral membrane protein appears to be a new participant in the calcium signal transduction pathway, implicating cyclophilin B in calcium signaling, even in the absence of cyclosporin.

Source: NCBI Gene 819 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation, type IIz (Limited, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 38 total
• Phenotypes (HPO): 14
• Cancer dependency (DepMap): dependent in 40.2% of screened cell lines
• MANE Select transcript: NM_001745

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1471
Approved symbol	CAMLG
Name	calcium modulating ligand
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	CAML, GET2
Ensembl gene	ENSG00000164615
Ensembl biotype	protein_coding
OMIM	601118
Entrez	819

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297156, ENST00000514518, ENST00000676819, ENST00000676829, ENST00000676928, ENST00000677273, ENST00000677966, ENST00000678434, ENST00000678771, ENST00000890609, ENST00000918598, ENST00000918599, ENST00000918600, ENST00000918601, ENST00000918602, ENST00000918603

RefSeq mRNA: 1 — MANE Select: NM_001745 NM_001745

CCDS: CCDS4178

Canonical transcript exons

ENST00000297156 — 4 exons

Exon	Start	End
ENSE00001085910	134741063	134741523
ENSE00001131668	134750759	134752157
ENSE00001131675	134738548	134738792
ENSE00003693007	134743987	134744052

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.9493 / max 276.1957, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58607	38.7237	1816
58606	5.2256	1712

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.36	gold quality
oocyte	CL:0000023	98.28	gold quality
cortical plate	UBERON:0005343	98.07	gold quality
sperm	CL:0000019	97.82	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.36	gold quality
cartilage tissue	UBERON:0002418	97.11	gold quality
trigeminal ganglion	UBERON:0001675	97.03	gold quality
calcaneal tendon	UBERON:0003701	97.03	gold quality
ganglionic eminence	UBERON:0004023	97.03	gold quality
superior vestibular nucleus	UBERON:0007227	97.02	gold quality
nipple	UBERON:0002030	96.98	gold quality
male germ cell	CL:0000015	96.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.90	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.88	gold quality
substantia nigra pars compacta	UBERON:0001965	96.85	gold quality
caput epididymis	UBERON:0004358	96.83	gold quality
mucosa of stomach	UBERON:0001199	96.77	gold quality
cauda epididymis	UBERON:0004360	96.71	gold quality
parietal pleura	UBERON:0002400	96.65	gold quality
ventral tegmental area	UBERON:0002691	96.63	gold quality
corpus epididymis	UBERON:0004359	96.56	gold quality
saphenous vein	UBERON:0007318	96.55	gold quality
entorhinal cortex	UBERON:0002728	96.52	gold quality
cranial nerve II	UBERON:0000941	96.47	gold quality
medulla oblongata	UBERON:0001896	96.43	gold quality
left ovary	UBERON:0002119	96.35	gold quality
nucleus accumbens	UBERON:0001882	96.29	gold quality
dorsal root ganglion	UBERON:0000044	96.23	gold quality
pons	UBERON:0000988	96.23	gold quality
middle temporal gyrus	UBERON:0002771	96.23	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	11.11
E-GEOD-100618	no	640.78
E-HCAD-6	no	285.81
E-HCAD-13	no	3.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting CAMLG, 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-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 40.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• CAMLG was more frequently significantly overexpressed in acute myeloid leukemia patients with CD56 immunophenoytpe (PMID:12031912)
• Kaposi’s sarcoma-associated herpesvirus mitochondrial K7 protein targets cellular CAML to increase the cytosolic Ca(2+) response, which consequently protects cells from mitochondrial damage and apoptosis (PMID:12388711)
• CAML is an important signal transducer for the actions of Ang II in regulating the calcineurin-NFAT pathway and the interaction of CAML with ATRAP may mediate the Ang II actions in vascular physiology (PMID:15668245)
• The intracellular C-terminus of fibrocystin interacts with CAML, a protein with an intracellular distribution that is similar to that of PKD2. (PMID:16243292)
• Binding of the MUC1 CT to CAML in human epithelial cells was confirmed by reciprocal coimmunoprecipitations, confocal microscopy, protein crosslinking, and coupled transcription/translation analyses. (PMID:19135167)
• Data show that tetherin restricts particle release and does not require CAML for this effect. (PMID:20126395)
• CAML was found to play a crucial role in the PRL/PRLR-dependent growth of breast cancer cells. (PMID:21128111)
• this study demonstrated that DENV manipulated the levels of CAML to subvert the apoptotic process which in turn favoured efficient virus production. (PMID:22281498)
• Results indicate calcium-modulating cyclophilin ligand (CAML) and WRB as components of the TRC40 receptor complex and a crucial mechanism for driving ER membrane insertion of TA proteins in mammalian cells. (PMID:23041287)
• Found that the calcium-modulating cyclophilin ligand (CAMLG), which is involved in Ca(2+) signaling, was the major host cell PilA binding protein. (PMID:23266901)
• A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells. (PMID:23879967)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	camlg	ENSDARG00000100409
mus_musculus	Caml	ENSMUSG00000021501
rattus_norvegicus	Camlg	ENSRNOG00000021911

Protein

Protein identifiers

Guided entry of tail-anchored proteins factor CAMLG — P49069 (reviewed: P49069)

Alternative names: Calcium signal-modulating cyclophilin ligand

All UniProt accessions (5): A0A7I2V377, A0A7I2V3C5, P49069, A0A7I2V518, D6RIW3

UniProt curated annotations — full annotation on UniProt →

Function. Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. Required for the stability of GET1. Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium. Essential for the survival of peripheral follicular B cells.

Subunit / interactions. Component of the Golgi to ER traffic (GET) complex, which is composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40. Within the complex, GET1 and CAMLG form a heterotetramer which is stabilized by phosphatidylinositol binding and which binds to the GET3 homodimer. Interacts (via C-terminus) with GET1. Interacts (via N-terminus) with GET3. GET3 shows a higher affinity for CAMLG than for GET1. Interacts (via N-terminus) with TNFRSF13B/TACI (via C-terminus). (Microbial infection) Interacts with human herpes virus 8/HHV-8 protein K7; this interaction modulates intracellular calcium concentration.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Highest levels in brain, testis and ovary.

Disease relevance. Congenital disorder of glycosylation 2Z (CDG2Z) [MIM:620201] 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. CDG2Z is an autosomal recessive form characterized by a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, CDG2Z is characterized by combined O- and N-linked glycosylation defects. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_001736* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016719	CAMLG	Family

Pfam: PF14963

UniProt features (21 total): topological domain 4, helix 4, transmembrane region 3, sequence variant 2, turn 2, chain 1, modified residue 1, disulfide bond 1, mutagenesis site 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8CR1	ELECTRON MICROSCOPY	3.2
6SO5	ELECTRON MICROSCOPY	4.2
8CR2	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49069-F1	62.66	0.03

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 (1): 55

Disulfide bonds (1): 208–284

Mutagenesis-validated functional residues (1):

Position	Phenotype
32–35	abolishes binding to get3.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane
R-HSA-9609507	Protein localization

MSigDB gene sets: 232 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_B_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, YY1_02, GOBP_PROTEIN_STABILIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY

GO Biological Process (11): B cell homeostasis (GO:0001782), receptor recycling (GO:0001881), defense response (GO:0006952), signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), vesicle-mediated transport (GO:0016192), negative regulation of protein ubiquitination (GO:0031397), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), protein insertion into ER membrane (GO:0045048), protein stabilization (GO:0050821), tail-anchored membrane protein insertion into ER membrane (GO:0071816)

GO Molecular Function (2): ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), GET complex (GO:0043529)

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 process	2
cellular anatomical structure	2
lymphocyte homeostasis	1
endocytosis	1
receptor metabolic process	1
response to stress	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ERBB signaling pathway	1
transport	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
endoplasmic reticulum organization	1
protein localization to organelle	1
protein insertion into membrane	1
regulation of protein stability	1
protein insertion into ER membrane	1
ubiquitin-like protein ligase binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum protein-containing complex	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMLG	TNFRSF13B	O14836	997
CAMLG	GET1	O00258	994
CAMLG	PPIB	P23284	961
CAMLG	AGTRAP	Q6RW13	843
CAMLG	GET3	O43681	831
CAMLG	TNFSF13B	Q9Y275	792
CAMLG	GET4	Q7L5D6	784
CAMLG	TNFRSF13C	Q96RJ3	783
CAMLG	UBL4A	P11441	736
CAMLG	BST2	Q10589	728
CAMLG	PKHD1	P08F94	724
CAMLG	SGTA	O43765	692
CAMLG	CHRM3	P20309	548
CAMLG	BSG	P35613	528
CAMLG	TNFRSF17	Q02223	507

IntAct

124 interactions, top by confidence:

A	B	Type	Score
CAMLG	GET3	psi-mi:“MI:0914”(association)	0.820
GET3	CAMLG	psi-mi:“MI:0915”(physical association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CAMLG	KCNA2	psi-mi:“MI:0915”(physical association)	0.670
KCNA2	CAMLG	psi-mi:“MI:0915”(physical association)	0.670
GET3	GET1	psi-mi:“MI:0914”(association)	0.640
EGFR	CAMLG	psi-mi:“MI:0915”(physical association)	0.630
CAMLG	GET1	psi-mi:“MI:0915”(physical association)	0.560
KCNA2	CAMLG	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	F11R	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	CAMLG	psi-mi:“MI:0915”(physical association)	0.560
	CAMLG	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	LCN2	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	ETNK1	psi-mi:“MI:0915”(physical association)	0.560
RPN1	CAMLG	psi-mi:“MI:0915”(physical association)	0.560
AGR2	CAMLG	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	HSP90B1	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	PBXIP1	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	KCNE4	psi-mi:“MI:0915”(physical association)	0.560
LAT	CAMLG	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (220): KCNA2 (Two-hybrid), CAMLG (Two-hybrid), WRB (Affinity Capture-MS), CAMLG (Proximity Label-MS), CAMLG (Proximity Label-MS), CAMLG (Proximity Label-MS), CAMLG (Proximity Label-MS), CAMLG (Proximity Label-MS), CAMLG (Proximity Label-MS), CAMLG (PCA), CAMLG (Affinity Capture-Luminescence), ASNA1 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), CAMLG (Affinity Capture-MS), CAMLG (Negative Genetic)

ESM2 similar proteins: A2BDB7, A2CE83, B2ZX90, D3IUT5, E1BXS0, F4IDY7, P0DPK0, P49069, P58501, Q07532, Q0P4A6, Q1JQE2, Q28GJ0, Q28GL6, Q2KJD6, Q2MJV9, Q2TBJ0, Q2WG79, Q2WG80, Q5F3D1, Q5R789, Q5TID7, Q5U3I2, Q5ZHQ6, Q640U0, Q641E3, Q66H73, Q67W65, Q68F53, Q6AYN9, Q6DRL4, Q6NZY4, Q7TPE5, Q7Z2Z1, Q7ZX27, Q80YR7, Q80ZU5, Q86XK3, Q8BQ33, Q8C6C7

Diamond homologs: P49069, P49070, Q6DGG9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CAMLG	“form complex”	“GET complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Regulation of RAS by GAPs	5	20.2×	9e-05
RAF/MAP kinase cascade	5	6.4×	5e-03
Neutrophil degranulation	8	3.9×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	5	14.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

438 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134738789:GCGG:G	donor_gain	1.0000
5:134738791:GG:G	donor_gain	1.0000
5:134738792:GG:G	donor_gain	1.0000
5:134738793:G:GA	donor_loss	1.0000
5:134738793:G:GG	donor_gain	1.0000
5:134738794:T:A	donor_loss	1.0000
5:134743985:A:AG	acceptor_gain	1.0000
5:134743986:G:GG	acceptor_gain	1.0000
5:134750755:ACAG:A	acceptor_loss	1.0000
5:134750756:CAGAG:C	acceptor_loss	1.0000
5:134750757:A:AG	acceptor_gain	1.0000
5:134750758:G:GG	acceptor_gain	1.0000
5:134750758:GA:G	acceptor_gain	1.0000
5:134750758:GAGT:G	acceptor_gain	1.0000
5:134741061:A:AG	acceptor_gain	0.9900
5:134741062:G:GG	acceptor_gain	0.9900
5:134743986:GTCC:G	acceptor_gain	0.9900
5:134750754:CACA:C	acceptor_loss	0.9900
5:134750755:A:AG	acceptor_gain	0.9900
5:134750756:C:G	acceptor_gain	0.9900
5:134750757:AGAGT:A	acceptor_gain	0.9900
5:134750758:GAGTG:G	acceptor_gain	0.9900
5:134741062:GAA:G	acceptor_gain	0.9800
5:134750753:A:AG	acceptor_gain	0.9800
5:134750754:C:G	acceptor_gain	0.9800
5:134738790:CGG:C	donor_gain	0.9700
5:134738791:GGG:G	donor_gain	0.9700
5:134738788:CGCGG:C	donor_gain	0.9600
5:134738789:GCGGG:G	donor_gain	0.9600
5:134741521:TTGGT:T	donor_loss	0.9500

AlphaMissense

1918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134738727:T:C	L36P	1.000
5:134744018:T:C	L222P	1.000
5:134750799:T:A	L247H	1.000
5:134750799:T:C	L247P	1.000
5:134738714:C:A	R32S	0.999
5:134738727:T:A	L36Q	0.999
5:134738730:T:C	L37P	0.999
5:134738739:C:G	S40W	0.999
5:134738747:C:A	R43S	0.999
5:134738760:T:C	I47T	0.999
5:134738760:T:G	I47S	0.999
5:134741473:G:A	G195R	0.999
5:134741473:G:C	G195R	0.999
5:134743991:T:A	I213K	0.999
5:134743997:C:A	A215D	0.999
5:134744000:C:A	P216Q	0.999
5:134744000:C:G	P216R	0.999
5:134744006:T:A	L218H	0.999
5:134744006:T:C	L218P	0.999
5:134744018:T:A	L222H	0.999
5:134744029:G:A	G226R	0.999
5:134744029:G:C	G226R	0.999
5:134750793:C:A	A245D	0.999
5:134750796:C:A	A246E	0.999
5:134750802:T:C	L248P	0.999
5:134750805:T:C	L249S	0.999
5:134750810:G:A	G251R	0.999
5:134750810:G:C	G251R	0.999
5:134750811:G:A	G251E	0.999
5:134750811:G:T	G251V	0.999

dbSNP variants (sampled 300 via entrez): RS1000686100 (5:134740335 A>G), RS1000823516 (5:134740548 T>G), RS1000970115 (5:134738193 TG>T,TGG), RS1001366238 (5:134736882 T>C), RS1001527302 (5:134750245 A>G,T), RS1001596302 (5:134742888 G>A), RS1001748420 (5:134749330 A>C), RS1001759105 (5:134743237 G>T), RS1002403127 (5:134738110 C>G,T), RS1002532019 (5:134751974 A>G), RS1002628560 (5:134752242 G>A), RS1002885293 (5:134737887 G>A,C), RS1002970622 (5:134740788 T>G), RS1003709842 (5:134738383 T>C,G), RS1004204726 (5:134746984 T>C)

Disease associations

OMIM: gene MIM:601118 | disease phenotypes: MIM:620201

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital disorder of glycosylation, type IIz	Limited	AR

Mondo (1): congenital disorder of glycosylation, type IIz (MONDO:0859357)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0002169	Clonus
HP:0002376	Developmental regression
HP:0002421	Poor head control
HP:0003121	Limb joint contracture
HP:0003593	Infantile onset
HP:0008936	Axial hypotonia
HP:0011471	Gastrostomy tube feeding in infancy
HP:0012301	Type II transferrin isoform profile
HP:0033725	Thin corpus callosum
HP:0034353	Appendicular spasticity
HP:0100275	Diffuse cerebellar atrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000175_35	Height	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	4
Cyclosporine	decreases methylation, increases expression	3
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
chloropicrin	affects expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Biological Factors	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects expression	1
Cycloheximide	increases expression, decreases reaction	1

Clinical trials (associated diseases)

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