ALG12

Summary

ALG12 (ALG12 alpha-1,6-mannosyltransferase, HGNC:19358) is a protein-coding gene on chromosome 22q13.33, encoding Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase (Q9BV10). Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.

This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation.

Source: NCBI Gene 79087 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ALG12-congenital disorder of glycosylation (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 798 total — 24 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 119
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_024105

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19358
Approved symbol	ALG12
Name	ALG12 alpha-1,6-mannosyltransferase
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	ECM39, CDG1G
Ensembl gene	ENSG00000182858
Ensembl biotype	protein_coding
OMIM	607144
Entrez	79087

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000330817, ENST00000486602, ENST00000492791, ENST00000905516, ENST00000905517, ENST00000905518, ENST00000905519, ENST00000905520, ENST00000930042, ENST00000967561

RefSeq mRNA: 1 — MANE Select: NM_024105 NM_024105

CCDS: CCDS14081

Canonical transcript exons

ENST00000330817 — 10 exons

Exon	Start	End
ENSE00001330529	49900229	49904066
ENSE00001427144	49918263	49918438
ENSE00002216882	49910434	49910607
ENSE00002249644	49913385	49913517
ENSE00002250898	49909894	49910088
ENSE00002270589	49913604	49913843
ENSE00002441975	49904337	49904506
ENSE00002454355	49909244	49909347
ENSE00002529719	49907721	49907944
ENSE00003463237	49904179	49904254

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 87.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.4467 / max 58.7314, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194675	7.9485	1766
194673	3.9479	1596
194674	0.5503	321

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	87.72	gold quality
stromal cell of endometrium	CL:0002255	87.28	gold quality
left lobe of thyroid gland	UBERON:0001120	86.13	gold quality
apex of heart	UBERON:0002098	85.99	gold quality
body of stomach	UBERON:0001161	85.69	gold quality
right lobe of liver	UBERON:0001114	85.40	gold quality
mucosa of transverse colon	UBERON:0004991	85.12	gold quality
thyroid gland	UBERON:0002046	85.06	gold quality
granulocyte	CL:0000094	84.85	gold quality
metanephros cortex	UBERON:0010533	84.54	gold quality
triceps brachii	UBERON:0001509	84.29	gold quality
body of pancreas	UBERON:0001150	83.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.69	gold quality
transverse colon	UBERON:0001157	83.64	gold quality
minor salivary gland	UBERON:0001830	83.60	gold quality
right adrenal gland	UBERON:0001233	83.51	gold quality
saliva-secreting gland	UBERON:0001044	83.48	gold quality
left adrenal gland	UBERON:0001234	83.40	gold quality
stomach	UBERON:0000945	83.36	gold quality
thoracic aorta	UBERON:0001515	83.29	gold quality
ascending aorta	UBERON:0001496	83.25	gold quality
mucosa of stomach	UBERON:0001199	83.17	gold quality
heart left ventricle	UBERON:0002084	82.91	gold quality
lower esophagus	UBERON:0013473	82.89	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.89	gold quality
left adrenal gland cortex	UBERON:0035825	82.88	gold quality
left uterine tube	UBERON:0001303	82.84	gold quality
vena cava	UBERON:0004087	82.82	gold quality
gluteal muscle	UBERON:0002000	82.81	silver quality
cardiac ventricle	UBERON:0002082	82.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF6, ETS1, YY1

miRNA regulators (miRDB)

24 targeting ALG12, 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-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-495-5P	97.62	68.28	682
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-582-3P	96.69	67.38	1019

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• deficiency results in congenital disorders of glycosylation type Ig (PMID:11983712)
• this enzyme has a role in glycosylation and its deficiency causes congenital disorder of glycosylation type Ig (PMID:12093361)
• As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and it is associated with distinct, abnormal glycosylation of total serum and IgG N-glycans (PMID:31529350)
• Novel ALG12 variants and hydronephrosis in siblings with impaired N-glycosylation. (PMID:34092405)
• A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient’s serum. (PMID:34467644)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alg12	ENSDARG00000041199
mus_musculus	Alg12	ENSMUSG00000035845
rattus_norvegicus	Alg12	ENSRNOG00000004591
drosophila_melanogaster	Alg12	FBGN0037743
caenorhabditis_elegans		WBGENE00022629

Paralogs (2): PIGB (ENSG00000069943), ALG9 (ENSG00000086848)

Protein

Protein identifiers

Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase — Q9BV10 (reviewed: Q9BV10)

Alternative names: Asparagine-linked glycosylation protein 12 homolog, Dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferase, Mannosyltransferase ALG12 homolog, Membrane protein SB87

All UniProt accessions (3): Q9BV10, H7C4I6, H7C5R7

UniProt curated annotations — full annotation on UniProt →

Function. Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. In the lumen of the endoplasmic reticulum, adds the eighth mannose residue in an alpha-1,6 linkage onto Man(7)GlcNAc(2)-PP-dolichol to produce Man(8)GlcNAc(2)-PP-dolichol.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Congenital disorder of glycosylation 1G (CDG1G) [MIM:607143] A form of congenital disorder of glycosylation, a multisystem disorder 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. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 22 family.

RefSeq proteins (1): NP_077010* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005599	GPI_mannosylTrfase	Family

Pfam: PF03901

Enzyme classification (BRENDA):

• EC 2.4.1.260 — dolichyl-P-Man:Man7GlcNAc2-PP-dolichol alpha-1,6-mannosyltransferase (BRENDA: 5 organisms, 1 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• an alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = an alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:29535)

UniProt features (21 total): transmembrane region 12, sequence variant 7, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV10-F1	93.26	0.86

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-4720489	Defective ALG12 causes CDG-1g
R-HSA-1643685	Disease
R-HSA-3781860	Diseases associated with N-glycosylation of proteins
R-HSA-3781865	Diseases of glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 346 (showing top): GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KEGG_N_GLYCAN_BIOSYNTHESIS, YY1_Q6, MODULE_503, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, NIKOLSKY_BREAST_CANCER_22Q13_AMPLICON, GOBP_PROTEIN_MATURATION, MODULE_195, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_FOLDING, MODULE_147, MODULE_356, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_LUMENAL_SIDE_OF_MEMBRANE

GO Biological Process (4): protein folding (GO:0006457), protein N-linked glycosylation (GO:0006487), dolichol-linked oligosaccharide biosynthetic process (GO:0006488), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (5): alpha-1,6-mannosyltransferase activity (GO:0000009), mannosyltransferase activity (GO:0000030), dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity (GO:0052917), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), lumenal side of endoplasmic reticulum membrane (GO:0098553)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Asparagine N-linked glycosylation	1
Diseases associated with N-glycosylation of proteins	1
Diseases of glycosylation	1
Diseases of metabolism	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
glycoprotein biosynthetic process	1
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
mannosyltransferase activity	1
hexosyltransferase activity	1
alpha-1,6-mannosyltransferase activity	1
GlcNAc(2)-PP-Dol mannosyltransferase activity	1
catalytic activity	1
transferase activity	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
cellular anatomical structure	1
endoplasmic reticulum membrane	1
lumenal side of membrane	1

Protein interactions and networks

STRING

1322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALG12	ALG6	Q9Y672	899
ALG12	ALG3	Q92685	881
ALG12	ALG8	Q9BVK2	872
ALG12	SHANK3	Q9BYB0	819
ALG12	ALG11	Q2TAA5	796
ALG12	ALG1	Q9BT22	785
ALG12	RABL2B	Q9UNT1	777
ALG12	DPM1	O60762	771
ALG12	ALG13	Q9NP73	760
ALG12	RABL2A	Q9UBK7	752
ALG12	DPAGT1	Q9H3H5	744
ALG12	ALG14	Q96F25	736
ALG12	ALG5	Q9Y673	731
ALG12	MPI	P34949	704
ALG12	ALG2	Q9H553	689

IntAct

26 interactions, top by confidence:

A	B	Type	Score
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
PI4K2A	GABARAP	psi-mi:“MI:0914”(association)	0.530
ALG12	NUP35	psi-mi:“MI:0915”(physical association)	0.400
PRDX4	ALG12	psi-mi:“MI:0915”(physical association)	0.370
ALG12	RPL13A	psi-mi:“MI:0915”(physical association)	0.370
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
ASIC4	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
WDR4	PBX2	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
GGT7	ENTPD6	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
SLC39A12		psi-mi:“MI:0914”(association)	0.350
CHST5	SETD1A	psi-mi:“MI:0914”(association)	0.350
SLC28A2	EMC8	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), NUP35 (Affinity Capture-MS), ALG12 (Affinity Capture-RNA), ALG12 (Negative Genetic), ALG12 (Negative Genetic), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), ALG12 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNG2, O60725, O75908, O77759, O88269, O88908, O95255, Q0P4J9, Q290J8, Q3T1L5, Q3TAE8, Q3UV71, Q499P8, Q49LS7, Q4R4E1, Q4VV71, Q5F380, Q5KR61, Q5R8F6, Q5RAH7, Q5RKL5, Q6AZ83, Q6NVG1, Q7SXZ1, Q7T310, Q7TPN3, Q7TQM4, Q86VD9, Q8AVI9, Q8BTP0, Q8C0T0, Q8C3X8, Q8CI59, Q8IUR5, Q8K2A8, Q8L638, Q8R1J1, Q8R4P9

Diamond homologs: A8MR93, P53730, Q23361, Q4V7R2, Q8VDB2, Q9BV10, Q9USD4, Q9VH78, Q7SXZ1, Q1LZA0, Q6CAB8, Q92521, Q4IB63, Q5AK24, P30777, Q9JJQ0, C6Y4A9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	17
Uncertain significance	404
Likely benign	249
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1383200	NM_024105.4(ALG12):c.522G>A (p.Trp174Ter)	Pathogenic
1440773	NM_024105.4(ALG12):c.789C>A (p.Tyr263Ter)	Pathogenic
1448154	NM_024105.4(ALG12):c.502G>T (p.Glu168Ter)	Pathogenic
1456464	NM_024105.4(ALG12):c.688dup (p.Tyr230fs)	Pathogenic
2073899	NM_024105.4(ALG12):c.336G>A (p.Trp112Ter)	Pathogenic
2090231	NM_024105.4(ALG12):c.1129C>T (p.Gln377Ter)	Pathogenic
2103386	NM_024105.4(ALG12):c.424_428delinsCAGTTCCAC (p.Phe142fs)	Pathogenic
2426800	NC_000022.10:g.(?50297486)(50307413_?)del	Pathogenic
242855	NM_024105.4(ALG12):c.117del (p.Gln40fs)	Pathogenic
2697267	NM_024105.4(ALG12):c.698_699del (p.Arg233fs)	Pathogenic
2734803	NM_024105.4(ALG12):c.731G>A (p.Trp244Ter)	Pathogenic
2824299	NM_024105.4(ALG12):c.160C>T (p.Gln54Ter)	Pathogenic
2839616	NM_024105.4(ALG12):c.21_33dup (p.Leu12fs)	Pathogenic
3358165	NM_024105.4(ALG12):c.604C>T (p.Arg202Ter)	Pathogenic
3391942	GRCh37/hg19 22q13.2-13.33(chr22:43451317-50307583)x1	Pathogenic
3437	NM_024105.4(ALG12):c.473T>C (p.Leu158Pro)	Pathogenic
3438	NM_024105.4(ALG12):c.1242C>G (p.Tyr414Ter)	Pathogenic
3617623	NM_024105.4(ALG12):c.755del (p.Ser252fs)	Pathogenic
3688618	NM_024105.4(ALG12):c.1015_1016del (p.Trp339fs)	Pathogenic
4697444	NM_024105.4(ALG12):c.861del (p.Thr288fs)	Pathogenic
4767896	NM_024105.4(ALG12):c.904_908del (p.Tyr302fs)	Pathogenic
560937	NM_024105.4(ALG12):c.930_931del (p.Arg311fs)	Pathogenic
599527	NM_014838.3(ZBED4):c.172C>T (p.Arg58Ter)	Pathogenic
987881	NM_024105.4(ALG12):c.165C>A (p.Tyr55Ter)	Pathogenic
1323878	NM_024105.4(ALG12):c.768+1G>A	Likely pathogenic
1698031	NM_024105.4(ALG12):c.687_688del (p.Tyr230fs)	Likely pathogenic
2093729	NM_024105.4(ALG12):c.439_469+19del	Likely pathogenic
2189336	NM_024105.4(ALG12):c.664+1G>A	Likely pathogenic
253336	GRCh37/hg19 22q13.31-13.33(chr22:46316673-50357320)x1	Likely pathogenic
3433	NM_024105.4(ALG12):c.424T>G (p.Phe142Val)	Likely pathogenic

SpliceAI

2219 predictions. Top by Δscore:

Variant	Effect	Δscore
22:49904252:CGT:C	acceptor_gain	1.0000
22:49904502:TCAGC:T	acceptor_gain	1.0000
22:49904503:CAGC:C	acceptor_gain	1.0000
22:49904503:CAGCC:C	acceptor_gain	1.0000
22:49904504:AGC:A	acceptor_gain	1.0000
22:49904505:GC:G	acceptor_gain	1.0000
22:49904506:CC:C	acceptor_gain	1.0000
22:49904507:C:CC	acceptor_gain	1.0000
22:49904507:CTGA:C	acceptor_loss	1.0000
22:49909245:C:CA	donor_gain	1.0000
22:49909246:C:A	donor_gain	1.0000
22:49909292:T:A	donor_gain	1.0000
22:49909890:TTAC:T	donor_loss	1.0000
22:49909891:TACCT:T	donor_loss	1.0000
22:49909892:A:AC	donor_gain	1.0000
22:49909892:ACCT:A	donor_loss	1.0000
22:49909893:C:CG	donor_gain	1.0000
22:49909893:CCT:C	donor_gain	1.0000
22:49909893:CCTAA:C	donor_gain	1.0000
22:49910084:CAGGA:C	acceptor_gain	1.0000
22:49910085:AGGA:A	acceptor_gain	1.0000
22:49910086:GGA:G	acceptor_gain	1.0000
22:49910087:GA:G	acceptor_gain	1.0000
22:49910088:AC:A	acceptor_loss	1.0000
22:49910089:C:CC	acceptor_gain	1.0000
22:49910089:CTGCA:C	acceptor_loss	1.0000
22:49910099:G:C	acceptor_gain	1.0000
22:49910430:GTACC:G	donor_loss	1.0000
22:49910431:TA:T	donor_loss	1.0000
22:49910432:A:AC	donor_gain	1.0000

AlphaMissense

3092 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:49907777:G:C	F312L	0.996
22:49907777:G:T	F312L	0.996
22:49907779:A:G	F312L	0.996
22:49913500:G:C	F60L	0.994
22:49913500:G:T	F60L	0.994
22:49913502:A:G	F60L	0.994
22:49907789:C:A	K308N	0.992
22:49907789:C:G	K308N	0.992
22:49910007:C:A	R184M	0.992
22:49910489:G:C	F138L	0.991
22:49910489:G:T	F138L	0.991
22:49910491:A:G	F138L	0.991
22:49913655:G:C	F37L	0.991
22:49913655:G:T	F37L	0.991
22:49913657:A:G	F37L	0.991
22:49913658:G:C	S36R	0.990
22:49913658:G:T	S36R	0.990
22:49913660:T:G	S36R	0.990
22:49904202:A:C	F405L	0.988
22:49904202:A:T	F405L	0.988
22:49904204:A:G	F405L	0.988
22:49909303:A:G	W237R	0.988
22:49909303:A:T	W237R	0.988
22:49909330:C:G	D228H	0.986
22:49910477:G:C	F142L	0.986
22:49910477:G:T	F142L	0.986
22:49910479:A:G	F142L	0.986
22:49909274:G:C	N246K	0.985
22:49909274:G:T	N246K	0.985
22:49913662:T:A	E35V	0.985

dbSNP variants (sampled 300 via entrez): RS1000005513 (22:49900738 G>A,C), RS1000111270 (22:49861578 C>T), RS1000129127 (22:49872619 T>A), RS1000149486 (22:49879006 G>T), RS1000163812 (22:49861390 C>T), RS1000266567 (22:49905944 A>G), RS1000333191 (22:49863338 T>G), RS1000339018 (22:49898754 C>T), RS1000386793 (22:49899034 G>A,C), RS1000502121 (22:49862327 T>G), RS1000605752 (22:49859233 T>A,C), RS1000612542 (22:49891519 C>G), RS1000613309 (22:49896145 G>A), RS1000618046 (22:49893653 G>T), RS1000747364 (22:49864864 T>A)

Disease associations

OMIM: gene MIM:607144 | disease phenotypes: MIM:607143

GenCC curated gene-disease

Disease	Classification	Inheritance
ALG12-congenital disorder of glycosylation	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ALG12-congenital disorder of glycosylation	Definitive	AR

Mondo (1): ALG12-congenital disorder of glycosylation (MONDO:0011783)

Orphanet (1): ALG12-CDG (Orphanet:79324)

HPO phenotypes

119 total (30 of 119 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000119	Abnormality of the genitourinary system
HP:0000219	Thin upper lip vermilion
HP:0000253	Progressive microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000445	Wide nose
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000541	Retinal detachment
HP:0000750	Delayed speech and language development
HP:0000759	Abnormal peripheral nervous system morphology
HP:0000773	Short ribs
HP:0000969	Edema
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002481_12	Acne (severe)	4.000000e-06
GCST90002401_283	Platelet distribution width	1.000000e-09
GCST90002402_654	Platelet count	1.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535745	Congenital disorder of glycosylation type 1G (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
bleomycetin	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1
Isoindoles	affects response to substance	1

Cellosaurus cell lines

4 cell lines: 2 finite cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_DA80	GM20100	Finite cell line	Male
CVCL_DA81	GM20101	Finite cell line	Male
CVCL_SC24	HAP1 ALG12 (-) 1	Cancer cell line	Male
CVCL_SC25	HAP1 ALG12 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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