ZFPL1

Summary

ZFPL1 (zinc finger protein like 1, HGNC:12868) is a protein-coding gene on chromosome 11q13.1, encoding Zinc finger protein-like 1 (O95159). Required for cis-Golgi integrity and efficient ER to Golgi transport.

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of DNA-templated transcription. Located in Golgi apparatus.

Source: NCBI Gene 7542 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_006782

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12868
Approved symbol	ZFPL1
Name	zinc finger protein like 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	D11S750, MCG4
Ensembl gene	ENSG00000162300
Ensembl biotype	protein_coding
OMIM	619397
Entrez	7542

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000294258, ENST00000453524, ENST00000525509, ENST00000526289, ENST00000526334, ENST00000526440, ENST00000526791, ENST00000526945, ENST00000528123, ENST00000530488, ENST00000530744, ENST00000531761, ENST00000532200, ENST00000533216, ENST00000650243, ENST00000890493, ENST00000890494, ENST00000890495

RefSeq mRNA: 1 — MANE Select: NM_006782 NM_006782

CCDS: CCDS8092

Canonical transcript exons

ENST00000294258 — 8 exons

Exon	Start	End
ENSE00001064006	65087316	65087433
ENSE00001193137	65087928	65088398
ENSE00003339797	65085115	65085226
ENSE00003480307	65086928	65087074
ENSE00003486301	65086415	65086608
ENSE00003523483	65084691	65084800
ENSE00003662280	65086720	65086792
ENSE00003841301	65084222	65084378

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 93.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.6227 / max 142.6121, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115022	24.7867	1821
115023	1.5057	1116
115024	0.3302	170

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	93.22	gold quality
stromal cell of endometrium	CL:0002255	92.82	gold quality
adenohypophysis	UBERON:0002196	92.56	gold quality
ascending aorta	UBERON:0001496	92.13	gold quality
thoracic aorta	UBERON:0001515	92.08	gold quality
aorta	UBERON:0000947	91.88	gold quality
popliteal artery	UBERON:0002250	91.87	gold quality
tibial artery	UBERON:0007610	91.86	gold quality
apex of heart	UBERON:0002098	91.74	gold quality
pituitary gland	UBERON:0000007	91.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.29	gold quality
right coronary artery	UBERON:0001625	91.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.12	gold quality
left coronary artery	UBERON:0001626	90.99	gold quality
transverse colon	UBERON:0001157	90.90	gold quality
lower esophagus	UBERON:0013473	90.88	gold quality
left adrenal gland cortex	UBERON:0035825	90.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.88	gold quality
granulocyte	CL:0000094	90.87	gold quality
body of uterus	UBERON:0009853	90.87	gold quality
body of stomach	UBERON:0001161	90.86	gold quality
left adrenal gland	UBERON:0001234	90.84	gold quality
right adrenal gland	UBERON:0001233	90.72	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.72	gold quality
endocervix	UBERON:0000458	90.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.70	gold quality
lower esophagus mucosa	UBERON:0035834	90.67	gold quality
skin of leg	UBERON:0001511	90.66	gold quality
descending thoracic aorta	UBERON:0002345	90.63	gold quality
left uterine tube	UBERON:0001303	90.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting ZFPL1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-193A-5P	95.70	65.33	613
HSA-MIR-8071	95.69	64.93	484
HSA-MIR-7704	95.30	62.35	115

Literature-anchored findings (GeneRIF, showing 3)

• These data suggest that ZFPL1 has an important function in maintaining the integrity of the cis-Golgi and that it does so through interactions with GM130. (PMID:18323775)
• These results suggest that ZFPL1 may serve an important role in regulating autophagy in NCIN87 and BGC823 cells. (PMID:28447717)
• The RING domain was essential for the function of ZFPL1. (PMID:30036656)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfpl1	ENSDARG00000103453
mus_musculus	Zfpl1	ENSMUSG00000024792
rattus_norvegicus	Zfpl1	ENSRNOG00000050180
drosophila_melanogaster	CG5382	FBGN0038950
caenorhabditis_elegans		WBGENE00021563

Protein

Protein identifiers

Zinc finger protein-like 1 — O95159 (reviewed: O95159)

Alternative names: Zinc finger protein MCG4

All UniProt accessions (9): A0A0G2JKQ6, E9PJ47, E9PJX1, E9PMQ3, E9PNY1, E9PQ47, E9PQA5, O95159, H0YCU8

UniProt curated annotations — full annotation on UniProt →

Function. Required for cis-Golgi integrity and efficient ER to Golgi transport. Involved in the maintenance of the integrity of the cis-Golgi, possibly via its interaction with GOLGA2/GM130.

Subunit / interactions. Interacts with GOLGA2/GM130.

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

Tissue specificity. Expressed strongly in the exocrine pancreas.

Post-translational modifications. Phosphorylated.

Domain organisation. The B box-type and RING-type zinc fingers although degenerate play a central role in function of the protein.

Similarity. Belongs to the ZFPL1 family.

RefSeq proteins (1): NP_006773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR039043	ZFPL1	Family
IPR058730	U-box_ZFPL1-like	Domain
IPR058731	Znf-B_box_ZFPL1-like	Domain

Pfam: PF25993, PF25998

UniProt features (14 total): topological domain 2, mutagenesis site 2, sequence conflict 2, zinc finger region 2, compositionally biased region 2, chain 1, transmembrane region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95159-F1	74.72	0.43

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
27	impairs the interaction with olga2/gm130 and cis-golgi assembly.
53	impairs the interaction with olga2/gm130 and cis-golgi assembly.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): MORF_SNRP70, MORF_UBE2I, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, chr11q13, BROWNE_HCMV_INFECTION_48HR_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_PDPK1, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, MORF_IKBKG, DANG_BOUND_BY_MYC, MORF_ORC1L, MARSON_BOUND_BY_E2F4_UNSTIMULATED, MORF_MYST2, BENPORATH_MYC_MAX_TARGETS

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transport	1
cellular process	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
cytoplasm	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFPL1	VEGFB	P49765	736
ZFPL1	GOLGA5	Q8TBA6	567
ZFPL1	MEN1	O00255	563
ZFPL1	TMF1	P82094	538
ZFPL1	MGAT1	P26572	476
ZFPL1	TM9SF3	Q9HD45	469
ZFPL1	TBC1D23	Q9NUY8	460
ZFPL1	TRIP11	Q15643	448
ZFPL1	PITPNM1	O00562	440
ZFPL1	STX5	Q13190	428
ZFPL1	ADSL	P30566	425
ZFPL1	ERC1	Q8IUD2	418
ZFPL1	GOLGA2	Q08379	413
ZFPL1	GALNT2	Q10471	406
ZFPL1	GOLGB1	Q14789	399
ZFPL1	C17orf75	Q9HAS0	399

IntAct

279 interactions, top by confidence:

A	B	Type	Score
ZFPL1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.740
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
ZFPL1	TEX29	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	SHISAL1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	SLC19A3	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	FATE1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	STX4	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	MFF	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	STX1A	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	TSTD2	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	KASH5	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	LDLRAD1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	STX2	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	ZFPL1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	CLEC10A	psi-mi:“MI:0915”(physical association)	0.560
FRMD3	ZFPL1	psi-mi:“MI:0915”(physical association)	0.560
	ZFPL1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (513): ZFPL1 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), ZFPL1 (Co-fractionation), ZFPL1 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), ERGIC2 (Affinity Capture-MS), OSBPL6 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), PPP2R5E (Affinity Capture-MS)

ESM2 similar proteins: A1L188, A2AMZ4, A2XK00, A7YY73, B4FGS2, B4FTR7, B8B624, C0HAV3, C5E268, G2TRP6, O13973, O75012, O95159, O95872, Q0VDN7, Q12894, Q28H71, Q2YDD3, Q3SZA2, Q3SZW4, Q3U0S6, Q3UJV1, Q49AH0, Q4G012, Q5FVV3, Q5U509, Q5U651, Q61858, Q6ASS9, Q6P0I6, Q756Q5, Q7S4Y4, Q7XAM0, Q7XK12, Q8BGD8, Q8BGX2, Q8CC36, Q8VED2, Q96BP2, Q96C34

Diamond homologs: A1L2S8, A7S7Z9, A8X2R2, B3P7K6, O95159, P62447, Q0VFM0, Q16N38, Q298N4, Q2YDD3, Q551M4, Q9DB43, Q9N4Y9, Q9VD26, Q9XF63, E9QAU8, Q6ZSG1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	ZFPL1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1079 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65084361:G:GG	donor_gain	1.0000
11:65084688:CAG:C	acceptor_loss	1.0000
11:65084815:G:T	donor_gain	1.0000
11:65085111:CCAGT:C	acceptor_loss	1.0000
11:65085112:CA:C	acceptor_loss	1.0000
11:65085113:A:AC	acceptor_loss	1.0000
11:65085113:A:AG	acceptor_gain	1.0000
11:65085114:G:A	acceptor_loss	1.0000
11:65085114:G:GA	acceptor_gain	1.0000
11:65085114:GT:G	acceptor_gain	1.0000
11:65085114:GTGC:G	acceptor_gain	1.0000
11:65086404:T:TA	acceptor_gain	1.0000
11:65086715:TCCA:T	acceptor_loss	1.0000
11:65086716:CCA:C	acceptor_loss	1.0000
11:65086718:A:AC	acceptor_loss	1.0000
11:65086718:A:AG	acceptor_gain	1.0000
11:65086719:G:GG	acceptor_gain	1.0000
11:65086719:GATC:G	acceptor_gain	1.0000
11:65086790:ATGGT:A	donor_loss	1.0000
11:65086792:GGTA:G	donor_loss	1.0000
11:65086793:G:GG	donor_gain	1.0000
11:65086794:T:A	donor_loss	1.0000
11:65086920:A:AG	acceptor_gain	1.0000
11:65086923:CACA:C	acceptor_loss	1.0000
11:65086925:CA:C	acceptor_loss	1.0000
11:65086926:A:AC	acceptor_loss	1.0000
11:65086926:A:AG	acceptor_gain	1.0000
11:65086927:G:GT	acceptor_gain	1.0000
11:65086927:GC:G	acceptor_gain	1.0000
11:65086927:GCC:G	acceptor_gain	1.0000

AlphaMissense

1994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65084741:T:C	F15L	1.000
11:65084743:C:A	F15L	1.000
11:65084743:C:G	F15L	1.000
11:65084744:T:C	C16R	1.000
11:65084746:C:G	C16W	1.000
11:65085139:T:A	W43R	1.000
11:65085139:T:C	W43R	1.000
11:65085141:G:C	W43C	1.000
11:65085141:G:T	W43C	1.000
11:65084702:G:A	G2R	0.999
11:65084702:G:C	G2R	0.999
11:65084708:T:A	C4S	0.999
11:65084708:T:C	C4R	0.999
11:65084709:G:A	C4Y	0.999
11:65084709:G:C	C4S	0.999
11:65084710:T:G	C4W	0.999
11:65084714:T:C	C6R	0.999
11:65084742:T:C	F15S	0.999
11:65084742:T:G	F15C	0.999
11:65084744:T:A	C16S	0.999
11:65084745:G:A	C16Y	0.999
11:65084745:G:C	C16S	0.999
11:65084745:G:T	C16F	0.999
11:65084747:T:C	F17L	0.999
11:65084749:C:A	F17L	0.999
11:65084749:C:G	F17L	0.999
11:65084766:T:A	V23D	0.999
11:65084768:T:A	C24S	0.999
11:65084768:T:C	C24R	0.999
11:65084769:G:A	C24Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000057588 (11:65087144 T>C,G), RS1000728244 (11:65085673 T>C), RS1001856820 (11:65086111 A>G), RS1003098812 (11:65087578 T>C), RS1003606382 (11:65082833 G>T), RS1003644024 (11:65082897 C>T), RS1003766030 (11:65088815 G>A,C,T), RS1004043791 (11:65083202 A>G), RS1005753275 (11:65083273 C>A,T), RS1006206034 (11:65084426 G>A), RS1006446533 (11:65084718 C>G,T), RS1006659505 (11:65087958 G>C,T), RS1007409768 (11:65082516 G>A), RS1007607650 (11:65088479 G>A,T), RS1008117439 (11:65085738 T>G)

Disease associations

OMIM: gene MIM:619397 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
Thiram	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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