MGAT4D

Summary

MGAT4D (MGAT4 family member D, HGNC:43619) is a protein-coding gene on chromosome 4q31.1, encoding Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase-like protein MGAT4D (A6NG13). May play a role in male spermatogenesis.

Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein N-linked glycosylation. Predicted to be located in Golgi membrane and endoplasmic reticulum membrane. Predicted to be active in Golgi stack; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment.

Source: NCBI Gene 152586 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001277353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:43619
Approved symbol	MGAT4D
Name	MGAT4 family member D
Location	4q31.1
Locus type	gene with protein product
Status	Approved
Aliases	GnT1IP
Ensembl gene	ENSG00000205301
Ensembl biotype	protein_coding
OMIM	610310
Entrez	152586

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000503109, ENST00000509091, ENST00000511113, ENST00000511632, ENST00000513018, ENST00000513106, ENST00000515121, ENST00000515354, ENST00000515402

RefSeq mRNA: 1 — MANE Select: NM_001277353 NM_001277353

CCDS: CCDS64066

Canonical transcript exons

ENST00000511113 — 11 exons

Exon	Start	End
ENSE00001619403	140479490	140479627
ENSE00001735229	140474813	140474946
ENSE00003462010	140456589	140456719
ENSE00003544914	140482327	140482485
ENSE00003564531	140459512	140459626
ENSE00003567414	140464896	140465009
ENSE00003638563	140461929	140462004
ENSE00003665489	140471775	140471821
ENSE00003684742	140451410	140451517
ENSE00003889124	140498129	140498293
ENSE00003913629	140442262	140443444

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 83.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0471 / max 46.9128, expressed in 5 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54125	0.0315	4
54126	0.0103	3
54127	0.0052	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	83.59	gold quality
right testis	UBERON:0004534	83.12	gold quality
testis	UBERON:0000473	80.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.79	gold quality
right uterine tube	UBERON:0001302	55.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.23	gold quality
cerebellar vermis	UBERON:0004720	46.54	gold quality
colonic epithelium	UBERON:0000397	46.48	gold quality
upper leg skin	UBERON:0004262	44.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
lower lobe of lung	UBERON:0008949	42.24	silver quality
quadriceps femoris	UBERON:0001377	41.99	gold quality
thymus	UBERON:0002370	41.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	41.69	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
nasal cavity mucosa	UBERON:0001826	41.14	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.55

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• The authors show here that the luminal domain of GnT1IP-L contains its MGAT1 inhibitory activity. (PMID:26371870)
• Point mutations that inactivate MGAT4D-L, an inhibitor of MGAT1 and complex N-glycan synthesis. (PMID:32763972)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:101663	ENSDARG00000037852
mus_musculus	Mgat4d	ENSMUSG00000035057
rattus_norvegicus	Mgat4d	ENSRNOG00000003695
drosophila_melanogaster	Mgat4a	FBGN0036446
drosophila_melanogaster	Mgat4b	FBGN0036447

Paralogs (3): MGAT4A (ENSG00000071073), MGAT4B (ENSG00000161013), MGAT4C (ENSG00000182050)

Protein

Protein identifiers

Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase-like protein MGAT4D — A6NG13 (reviewed: A6NG13)

Alternative names: N-acetylglucosaminyltransferase MGAT1 inhibitory protein

All UniProt accessions (6): A6NG13, D6RCD2, D6RCD3, D6RH02, D6RIE7, H0Y908

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in male spermatogenesis. In vitro acts as inhibitor of MGAT1 activity causing cell surface proteins to carry mainly high mannose N-glycans. The function is mediated by its lumenal domain and occurs specifically in the Golgi. A catalytic glucosyltransferase activity is not detected. May be involved in regulation of Sertoli-germ cell interactions during specific stages of spermatogenesis.

Subunit / interactions. May self-associate; specifically in the endoplasmic reticulum prior to its translocation to the Golgi. Interacts with MGAT1, MGAT3 and MAN2A2; may interact with MGTA1 specifically in the Golgi.

Subcellular location. Golgi apparatus membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in testis. Poorly expressed in testis biopsies from men with impaired spermatogenesis.

Similarity. Belongs to the glycosyltransferase 54 family.

RefSeq proteins (1): NP_001264282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006759	Glyco_transf_54	Family
IPR057279	MGAT4	Domain

Pfam: PF04666

UniProt features (8 total): glycosylation site 4, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NG13-F1	84.80	0.50

Functional residue map

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

Glycosylation sites (4): 54, 95, 144, 275

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_MALE_GAMETE_GENERATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLYCOPROTEIN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_GOLGI_STACK, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ENDOPLASMIC_RETICULUM_GOLGI_INTERMEDIATE_COMPARTMENT, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_UDP_GLYCOSYLTRANSFERASE_ACTIVITY

GO Biological Process (4): protein N-linked glycosylation (GO:0006487), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), obsolete negative regulation of protein glycosylation (GO:0060051)

GO Molecular Function (1): acetylglucosaminyltransferase activity (GO:0008375)

GO Cellular Component (7): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi stack (GO:0005795), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
intracellular membrane-bounded organelle	3
endomembrane system	2
glycoprotein biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Golgi apparatus subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGAT4D	C2orf80	Q0P641	662
MGAT4D	MGAT1	P26572	631
MGAT4D	FNDC8	Q8TC99	598
MGAT4D	C3orf22	Q8N5N4	544
MGAT4D	LRRC63	Q05C16	524
MGAT4D	ARHGAP42	A6NI28	509
MGAT4D	RNASE12	Q5GAN4	506
MGAT4D	SCOC	Q9UIL1	506
MGAT4D	C12orf56	Q8IXR9	505
MGAT4D	SMIM17	P0DL12	479
MGAT4D	SH2D7	A6NKC9	472
MGAT4D	ELMOD2	Q8IZ81	468
MGAT4D	MGAT2	Q10469	466
MGAT4D	C22orf42	Q6IC83	447
MGAT4D	CC2D2B	Q6DHV5	447
MGAT4D	C1orf167	Q5SNV9	447
MGAT4D	ANKRD62	A6NC57	447

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MGAT4D	HDLBP	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): HDLBP (Proximity Label-MS), MGAT4D (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2AJQ3, A2AUQ7, A5GFW8, A6NG13, A7RX69, D3ZNQ3, E1BPQ3, E9PU17, E9PX95, E9Q649, G3V9Q9, O15466, P0DN25, P23336, P27473, P38566, P38567, P48794, P61646, P97402, Q02742, Q09324, Q21389, Q2NKH9, Q2YDM8, Q3L7M0, Q3SX46, Q499P3, Q4R5T7, Q4V8F8, Q53G44, Q5U258, Q5ZLK4, Q6ZNI0, Q6ZXC8, Q71SG7, Q7Z388, Q7Z4J2, Q812F3, Q8BV66

Diamond homologs: A4IID1, A6NG13, O77836, Q4R4A8, Q4R854, Q4V8F8, Q5F407, Q5M854, Q5REP8, Q5U3T0, Q6GMK0, Q6GQI7, Q6ITT3, Q812F8, Q812G0, Q9D306, Q9D4R2, Q9DGD1, Q9UBM8, Q9UM21, Q9UQ53, A6H684

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1757 predictions. Top by Δscore:

Variant	Effect	Δscore
4:140498127:A:AC	donor_gain	1.0000
4:140498128:C:CC	donor_gain	1.0000
4:140498128:CTG:C	donor_gain	1.0000
4:140498128:CTGG:C	donor_gain	1.0000
4:140498128:CTGGT:C	donor_gain	1.0000
4:140498140:AT:A	donor_gain	1.0000
4:140456669:T:TC	acceptor_gain	0.9900
4:140482369:T:TA	donor_gain	0.9900
4:140495385:C:A	donor_gain	0.9900
4:140498122:CGCTT:C	donor_loss	0.9900
4:140498123:GCTTA:G	donor_loss	0.9900
4:140498124:CTTAC:C	donor_loss	0.9900
4:140498125:TTACT:T	donor_loss	0.9900
4:140498126:TACTG:T	donor_loss	0.9900
4:140498127:A:T	donor_loss	0.9900
4:140498128:C:CG	donor_loss	0.9900
4:140498128:CT:C	donor_gain	0.9900
4:140498141:T:TA	donor_gain	0.9900
4:140456668:A:C	acceptor_gain	0.9800
4:140479015:G:C	donor_gain	0.9800
4:140495384:T:TA	donor_gain	0.9800
4:140456580:AATAC:A	donor_loss	0.9700
4:140456581:ATAC:A	donor_loss	0.9700
4:140456582:TACT:T	donor_loss	0.9700
4:140456584:CTCA:C	donor_loss	0.9700
4:140456585:TCAC:T	donor_loss	0.9700
4:140456586:CACAA:C	donor_loss	0.9700
4:140456587:A:AC	donor_gain	0.9700
4:140456587:ACAA:A	donor_loss	0.9700
4:140456588:C:CC	donor_gain	0.9700

AlphaMissense

2491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:140459531:A:C	F286L	0.971
4:140459531:A:T	F286L	0.971
4:140459533:A:G	F286L	0.971
4:140456676:A:C	F307L	0.969
4:140456676:A:T	F307L	0.969
4:140456678:A:G	F307L	0.969
4:140459548:A:G	W281R	0.954
4:140459548:A:T	W281R	0.954
4:140456719:C:A	G293V	0.948
4:140456664:G:C	F311L	0.947
4:140456664:G:T	F311L	0.947
4:140456666:A:G	F311L	0.947
4:140461946:C:G	A249P	0.946
4:140461957:G:T	A245D	0.946
4:140451461:G:C	F355L	0.945
4:140451461:G:T	F355L	0.945
4:140451463:A:G	F355L	0.945
4:140474826:A:T	V171D	0.945
4:140474937:G:T	A134E	0.941
4:140456713:A:G	L295P	0.939
4:140456638:A:G	L320P	0.938
4:140465006:G:C	F192L	0.938
4:140465006:G:T	F192L	0.938
4:140465008:A:G	F192L	0.938
4:140456710:A:G	F296S	0.937
4:140461947:C:A	K248N	0.932
4:140461947:C:G	K248N	0.932
4:140456608:C:G	C330S	0.931
4:140456609:A:T	C330S	0.931
4:140461937:A:C	Y252D	0.931

dbSNP variants (sampled 300 via entrez): RS1000092316 (4:140482755 C>T), RS1000161671 (4:140490157 T>A), RS1000174487 (4:140461631 T>C,G), RS1000266237 (4:140475569 G>T), RS1000274886 (4:140455038 T>C), RS1000285285 (4:140468408 A>G), RS1000305930 (4:140455203 T>C), RS10003126 (4:140478455 T>C), RS1000356948 (4:140468753 A>G), RS1000526647 (4:140478235 A>G), RS1000531915 (4:140489180 T>C), RS1000635259 (4:140483225 T>C), RS1000648723 (4:140470073 A>C,G,T), RS1000660154 (4:140495768 G>A,T), RS1000680042 (4:140470394 A>C)

Disease associations

OMIM: gene MIM:610310 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Lipopolysaccharides	affects cotreatment, affects response to substance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation, increases methylation	1

Clinical trials (associated diseases)

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