YIPF3

Summary

YIPF3 (Yip1 domain family member 3, HGNC:21023) is a protein-coding gene on chromosome 6p21.1, encoding Protein YIPF3 (Q9GZM5). Involved in the maintenance of the Golgi structure.

Predicted to be involved in cell differentiation. Located in Golgi apparatus and transport vesicle.

Source: NCBI Gene 25844 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_015388

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21023
Approved symbol	YIPF3
Name	Yip1 domain family member 3
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp566C243, KLIP1, dJ337H4.3, FinGER3, Yip5b, YIPFbeta2
Ensembl gene	ENSG00000137207
Ensembl biotype	protein_coding
OMIM	609775
Entrez	25844

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 20 protein_coding, 7 retained_intron, 5 nonsense_mediated_decay

ENST00000372417, ENST00000372422, ENST00000416380, ENST00000455768, ENST00000460547, ENST00000460903, ENST00000488966, ENST00000490447, ENST00000500090, ENST00000502714, ENST00000503147, ENST00000503972, ENST00000506469, ENST00000510102, ENST00000511831, ENST00000512713, ENST00000514627, ENST00000882375, ENST00000882376, ENST00000882377, ENST00000882378, ENST00000882379, ENST00000882380, ENST00000940668, ENST00000940669, ENST00000940670, ENST00000940671, ENST00000940672, ENST00000940673, ENST00000940674, ENST00000952244, ENST00000952245

RefSeq mRNA: 1 — MANE Select: NM_015388 NM_015388

CCDS: CCDS4899

Canonical transcript exons

ENST00000372422 — 9 exons

Exon	Start	End
ENSE00002040654	43511832	43512315
ENSE00002085469	43516727	43516926
ENSE00003480248	43512761	43512874
ENSE00003553749	43513359	43513451
ENSE00003589108	43513069	43513200
ENSE00003626226	43513588	43513633
ENSE00003627635	43515595	43515701
ENSE00003635206	43512440	43512563
ENSE00003637828	43515889	43516095

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.8911 / max 446.0507, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73698	86.2520	1828
73697	1.9646	1192
73699	1.0364	705
73696	0.6651	423
73695	0.6422	322
73694	0.3308	162

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.36	gold quality
stromal cell of endometrium	CL:0002255	98.34	gold quality
right adrenal gland	UBERON:0001233	98.32	gold quality
right adrenal gland cortex	UBERON:0035827	98.30	gold quality
left adrenal gland	UBERON:0001234	98.16	gold quality
left adrenal gland cortex	UBERON:0035825	98.07	gold quality
body of stomach	UBERON:0001161	98.03	gold quality
minor salivary gland	UBERON:0001830	97.88	gold quality
adenohypophysis	UBERON:0002196	97.83	gold quality
cortical plate	UBERON:0005343	97.81	gold quality
ganglionic eminence	UBERON:0004023	97.65	gold quality
mucosa of transverse colon	UBERON:0004991	97.35	gold quality
right lobe of thyroid gland	UBERON:0001119	97.31	gold quality
left lobe of thyroid gland	UBERON:0001120	97.25	gold quality
endocervix	UBERON:0000458	97.23	gold quality
transverse colon	UBERON:0001157	97.18	gold quality
body of uterus	UBERON:0009853	97.18	gold quality
granulocyte	CL:0000094	97.17	gold quality
adrenal cortex	UBERON:0001235	97.17	gold quality
right ovary	UBERON:0002118	97.17	gold quality
left ovary	UBERON:0002119	97.15	gold quality
metanephros cortex	UBERON:0010533	97.15	gold quality
right coronary artery	UBERON:0001625	97.14	gold quality
right lung	UBERON:0002167	97.14	gold quality
apex of heart	UBERON:0002098	97.13	gold quality
gall bladder	UBERON:0002110	97.07	gold quality
upper lobe of left lung	UBERON:0008952	96.91	gold quality
adrenal gland	UBERON:0002369	96.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.88	gold quality
ectocervix	UBERON:0012249	96.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting YIPF3, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-647	97.73	67.79	927
HSA-MIR-550B-2-5P	96.56	64.61	646
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-4769-5P	95.37	66.09	570
HSA-MIR-4734	88.28	63.44	87

Literature-anchored findings (GeneRIF, showing 4)

• identification and characterization of KLIP-1, a novel transmembrane protein whose expression correlates with hematopoietic activity (PMID:12490290)
• YIPF3 is synthesized in the ER as a N-glycosylated form (40 kDa), is then O-glycosylated in the Golgi apparatus to become a lower mobility form (46 kDa) and finally becomes a higher mobility form cleaved at its C-terminal luminal domain (36 kDa). (PMID:21757827)
• The significance of YIPF3 protein for the maintenance of the morphology of the Golgi was tested by RNA interference, revealing a number of specific morphological changes to this organelle on their depletion. (PMID:27999994)
• Knockdown of YIPF1 and YIPF2, but not that of YIPF6, also reduced intracellular glycans in HT-29 cells. Thus, we confirmed that YIPF1, YIPF2, and YIPF6 play a significant role in supporting normal glycan synthesis (PMID:28286305)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	yipf3	ENSDARG00000020449
mus_musculus	Yipf3	ENSMUSG00000071074
rattus_norvegicus	Yipf3	ENSRNOG00000018998
caenorhabditis_elegans		WBGENE00013139

Paralogs (1): DTWD1 (ENSG00000104047)

Protein

Protein identifiers

Protein YIPF3 — Q9GZM5 (reviewed: Q9GZM5)

Alternative names: Killer lineage protein 1, Natural killer cell-specific antigen KLIP1, YIP1 family member 3

All UniProt accessions (8): Q9GZM5, D6RA04, D6RAY4, D6RBQ1, D6RFI3, D6RGY8, E7EQR8, H0Y9A1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maintenance of the Golgi structure. May play a role in hematopoiesis.

Subunit / interactions. Interacts with YIPF4 and YIPF5.

Subcellular location. Cell membrane. Cytoplasm. Golgi apparatus. cis-Golgi network membrane.

Tissue specificity. Expressed by nucleated hematopoietic cells (at protein level).

Post-translational modifications. N-glycosylated in the ER (40 kDa form I), then O-glycosylated in the Golgi apparatus (46 kDa form II), the C-terminal lumenal region is later removed in the Golgi apparatus to produce a 36 kDa form III. O-glycosylated with core 1-like and core 2-like glycans. O-glycan heterogeneity at Thr-346: HexNAc (minor), HexHexNAc (major), Hex1HexNAc2 (minor), Hex2HexNAc2 (minor) and dHex1Hex2HexNAc2 (minor).

Similarity. Belongs to the YIP1 family.

RefSeq proteins (1): NP_056203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051521	DTWD1/YIPF3	Family

UniProt features (27 total): topological domain 6, transmembrane region 5, glycosylation site 5, sequence conflict 4, chain 2, initiator methionine 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZM5-F1	71.23	0.30

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): 2

Glycosylation sites (5): 333, 334, 337, 339, 346

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): BROWNE_HCMV_INFECTION_48HR_DN, PARENT_MTOR_SIGNALING_UP, BLALOCK_ALZHEIMERS_DISEASE_DN, SCGGAAGY_ELK1_02, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, CSR_LATE_UP.V1_UP, DCA_UP.V1_DN, OISHI_CHOLANGIOMA_STEM_CELL_LIKE_UP, BANP_TARGET_GENES, CIITA_TARGET_GENES, DLX6_TARGET_GENES, DYRK1A_TARGET_GENES, HOXB4_TARGET_GENES, HOXC6_TARGET_GENES, IRF5_TARGET_GENES

GO Biological Process (1): cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), transport vesicle (GO:0030133), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
cellular anatomical structure	2
cellular developmental process	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cytoplasmic vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YIPF3	YIPF4	Q9BSR8	845
YIPF3	YIPF2	Q9BWQ6	810
YIPF3	YIPF1	Q9Y548	792
YIPF3	SCEL	O95171	711
YIPF3	YIPF6	Q96EC8	692
YIPF3	YIPF5	Q969M3	666
YIPF3	SYNPO	Q8N3V7	650
YIPF3	CYP26A1	O43174	649
YIPF3	SULF1	Q8IWU6	649
YIPF3	YIF1A	O95070	645
YIPF3	YIPF7	Q8N8F6	606
YIPF3	WT1	P19544	559
YIPF3	ACTN4	O43707	550
YIPF3	NPHS1	O60500	549
YIPF3	PAX2	Q02962	548

IntAct

188 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
YIPF3	YIPF4	psi-mi:“MI:0915”(physical association)	0.830
YIPF4	YIPF3	psi-mi:“MI:0915”(physical association)	0.830
KHDRBS2	KHDRBS3	psi-mi:“MI:0914”(association)	0.800
KRTAP3-2	YIPF3	psi-mi:“MI:0915”(physical association)	0.780
YIPF3	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.780
YIPF3	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
YIPF3	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
YIPF3	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	YIPF3	psi-mi:“MI:0915”(physical association)	0.560
	YIPF3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	YIPF3	psi-mi:“MI:0915”(physical association)	0.560
YIPF3	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (312): YIPF3 (Two-hybrid), KRTAP3-2 (Two-hybrid), YIPF4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), YIPF3 (Affinity Capture-MS), YIPF3 (Affinity Capture-MS), YIPF3 (Affinity Capture-MS), YIPF3 (Affinity Capture-MS), YIPF3 (Affinity Capture-MS), YIPF3 (Two-hybrid), YIPF4 (Two-hybrid), YIPF3 (Affinity Capture-MS)

ESM2 similar proteins: A1CJW1, A1D7K7, A3LU53, A4R0J5, A5DGY3, A6R3V7, A6ZV87, A7F5K4, A7TSA7, A9JTJ0, B2WDD8, B3LIC1, B4UN04, B8JLV7, O64614, P0CS24, P41806, Q08013, Q0CXF5, Q0UV26, Q28CH8, Q28GR4, Q2HDV5, Q3B8G4, Q3SZ87, Q3UDR8, Q42337, Q4V7U1, Q4V8S3, Q5BK13, Q5F384, Q5RAS8, Q5RCD7, Q5SYH2, Q5ZLL0, Q6BXM0, Q6CDK3, Q6CQP9, Q6TUD4, Q75EI3

Diamond homologs: Q3B8G4, Q3UDR8, Q5F384, Q6TUD4, Q803Z2, Q9GZM5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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
SLC-mediated transport of neurotransmitters	5	17.9×	2e-04
Amino acid transport across the plasma membrane	5	13.2×	8e-04
R-HSA-425366	7	11.1×	1e-04
Class A/1 (Rhodopsin-like receptors)	17	11.1×	5e-11
SLC transporter disorders	5	8.9×	4e-03
GPCR ligand binding	15	8.4×	4e-08
Chemokine receptors bind chemokines	5	8.2×	5e-03
SLC-mediated transmembrane transport	13	6.8×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	13	19.4×	4e-11
amino acid transport	9	19.1×	2e-07
positive regulation of cytosolic calcium ion concentration	17	13.5×	4e-12
phospholipase C-activating G protein-coupled receptor signaling pathway	15	13.4×	1e-10
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	6	12.7×	6e-04
calcium-mediated signaling	9	11.2×	2e-05
regulation of cell adhesion	5	10.4×	5e-03
transport across blood-brain barrier	8	9.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1169 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43512311:GATCC:G	acceptor_gain	1.0000
6:43512313:TCC:T	acceptor_gain	1.0000
6:43512313:TCCC:T	acceptor_loss	1.0000
6:43512314:CC:C	acceptor_gain	1.0000
6:43512314:CCC:C	acceptor_gain	1.0000
6:43512315:CC:C	acceptor_gain	1.0000
6:43512316:C:A	acceptor_loss	1.0000
6:43512316:C:CC	acceptor_gain	1.0000
6:43512316:C:T	acceptor_gain	1.0000
6:43512317:T:A	acceptor_loss	1.0000
6:43512433:CACTT:C	donor_loss	1.0000
6:43512434:ACTTA:A	donor_loss	1.0000
6:43512435:CTTA:C	donor_loss	1.0000
6:43512437:TAC:T	donor_loss	1.0000
6:43512438:A:AC	donor_gain	1.0000
6:43512438:AC:A	donor_gain	1.0000
6:43512439:C:CA	donor_loss	1.0000
6:43512439:C:CC	donor_gain	1.0000
6:43512439:CC:C	donor_gain	1.0000
6:43512439:CCCT:C	donor_gain	1.0000
6:43512564:C:CC	acceptor_gain	1.0000
6:43512564:CTAGG:C	acceptor_loss	1.0000
6:43512570:CCA:C	acceptor_gain	1.0000
6:43512870:TAGCC:T	acceptor_gain	1.0000
6:43513066:TA:T	donor_loss	1.0000
6:43513067:A:AC	donor_gain	1.0000
6:43513068:C:CC	donor_gain	1.0000
6:43513196:TCCCG:T	acceptor_gain	1.0000
6:43513197:CCCG:C	acceptor_gain	1.0000
6:43513197:CCCGC:C	acceptor_gain	1.0000

AlphaMissense

2266 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43512874:C:G	G223R	1.000
6:43513152:A:G	W195R	1.000
6:43513152:A:T	W195R	1.000
6:43513162:G:C	C191W	1.000
6:43513175:G:T	A187D	1.000
6:43513182:C:G	G185R	1.000
6:43513381:A:G	M171T	1.000
6:43513390:A:G	L168P	1.000
6:43513393:A:G	L167P	1.000
6:43513420:A:C	M158R	1.000
6:43513420:A:T	M158K	1.000
6:43513426:G:C	P156R	1.000
6:43513426:G:T	P156H	1.000
6:43513429:C:T	G155E	1.000
6:43513430:C:G	G155R	1.000
6:43513430:C:T	G155R	1.000
6:43513631:A:G	L133P	1.000
6:43513631:A:T	L133H	1.000
6:43515624:A:C	F122L	1.000
6:43515624:A:T	F122L	1.000
6:43515625:A:C	F122C	1.000
6:43515625:A:G	F122S	1.000
6:43515626:A:G	F122L	1.000
6:43515626:A:T	F122I	1.000
6:43515633:T:A	R119S	1.000
6:43515633:T:G	R119S	1.000
6:43515634:C:G	R119T	1.000
6:43515637:A:G	L118P	1.000
6:43515637:A:T	L118H	1.000
6:43515643:T:A	D116V	1.000

dbSNP variants (sampled 300 via entrez): RS1000176457 (6:43517809 C>G), RS1001734000 (6:43515697 C>T), RS1002063900 (6:43514483 C>T), RS1002090465 (6:43514236 A>G), RS1002281550 (6:43517792 G>C), RS1002731624 (6:43515101 C>G), RS1003141748 (6:43516910 G>A), RS1003284668 (6:43516652 A>G,T), RS1003950965 (6:43513989 C>G,T), RS1004141332 (6:43517346 A>G), RS1004994320 (6:43512065 G>A), RS1005030455 (6:43513757 G>A,C,T), RS1006036282 (6:43512422 G>C), RS1006147900 (6:43518452 G>T), RS1006198405 (6:43518373 T>C)

Disease associations

OMIM: gene MIM:609775 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	affects methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	decreases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Thapsigargin	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LI	Abcam HEK293T YIPF3 KO	Transformed cell line	Female
CVCL_D1J4	HEK293::TMEM192-3xHA YIPF4-/-;YIPF3-/-	Transformed cell line	Female
CVCL_D1J8	HeLa::TMEM192-3xHA YIPF3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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