ZPR1

Summary

ZPR1 (ZPR1 zinc finger, HGNC:13051) is a protein-coding gene on chromosome 11q23.3, encoding Zinc finger protein ZPR1 (O75312). Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8882 — RefSeq curated summary.

At a glance

• Gene–disease (curated): growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (Moderate, GenCC)
• GWAS associations: 121
• Clinical variants (ClinVar): 84 total — 1 pathogenic
• Phenotypes (HPO): 33
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_003904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13051
Approved symbol	ZPR1
Name	ZPR1 zinc finger
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109917
Ensembl biotype	protein_coding
OMIM	603901
Entrez	8882

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000227322, ENST00000366405, ENST00000425791, ENST00000429220, ENST00000431973, ENST00000444935, ENST00000449430, ENST00000487030, ENST00000498065, ENST00000900045, ENST00000900046, ENST00000900047, ENST00000900048, ENST00000900049, ENST00000932352, ENST00000932353

RefSeq mRNA: 2 — MANE Select: NM_003904 NM_001317086, NM_003904

CCDS: CCDS8375

Canonical transcript exons

ENST00000227322 — 14 exons

Exon	Start	End
ENSE00000747541	116779772	116779837
ENSE00000747545	116784378	116784448
ENSE00000747547	116784855	116784921
ENSE00000747548	116785099	116785146
ENSE00000747549	116785514	116785636
ENSE00001294966	116787820	116788023
ENSE00003483467	116787482	116787643
ENSE00003507870	116786969	116787059
ENSE00003553479	116786511	116786581
ENSE00003570550	116782919	116783029
ENSE00003587046	116783530	116783619
ENSE00003588747	116785796	116785882
ENSE00003597528	116782158	116782244
ENSE00003771780	116773799	116779059

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.1296 / max 168.3272, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122420	28.8203	1818
122421	0.3093	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.44	gold quality
ganglionic eminence	UBERON:0004023	94.21	gold quality
right testis	UBERON:0004534	93.84	gold quality
sperm	CL:0000019	93.75	gold quality
left testis	UBERON:0004533	93.67	gold quality
male germ cell	CL:0000015	93.44	gold quality
islet of Langerhans	UBERON:0000006	92.79	gold quality
sural nerve	UBERON:0015488	92.49	gold quality
adrenal tissue	UBERON:0018303	92.38	gold quality
testis	UBERON:0000473	92.15	gold quality
calcaneal tendon	UBERON:0003701	92.13	gold quality
body of pancreas	UBERON:0001150	91.67	gold quality
right lobe of liver	UBERON:0001114	91.37	gold quality
pancreas	UBERON:0001264	91.31	gold quality
smooth muscle tissue	UBERON:0001135	91.08	gold quality
gastrocnemius	UBERON:0001388	90.95	gold quality
granulocyte	CL:0000094	90.74	gold quality
ventricular zone	UBERON:0003053	90.68	gold quality
omental fat pad	UBERON:0010414	90.67	gold quality
peritoneum	UBERON:0002358	90.65	gold quality
stromal cell of endometrium	CL:0002255	90.64	gold quality
muscle of leg	UBERON:0001383	90.36	gold quality
pancreatic ductal cell	CL:0002079	90.22	silver quality
adipose tissue of abdominal region	UBERON:0007808	90.10	gold quality
popliteal artery	UBERON:0002250	90.08	gold quality
tibial artery	UBERON:0007610	90.06	gold quality
rectum	UBERON:0001052	89.93	gold quality
left coronary artery	UBERON:0001626	89.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.83	gold quality
aorta	UBERON:0000947	89.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	1634.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting ZPR1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-648	98.64	66.13	553
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-144-5P	97.66	69.90	531
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-602	97.09	61.68	156
HSA-MIR-301A-5P	96.88	68.07	931
HSA-MIR-301B-5P	96.88	67.75	946
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-345-5P	96.40	66.43	663

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 18)

• ZPR1 deficiency causes disruption of survival motor neurons and histone gene-specific transcription factor NPAT localization within the nucleus, blocks S phase progression, and arrests cells in both the G1 and G2 phases of the cell cycle. (PMID:17068332)
• Significant associations of two SNPs (rs964184 and rs12286037) from ZNF259 with triglyceride levels in an Asian Indian cohort. (PMID:22623978)
• genetic polymorphism at the loci is associated with Factor VII and fibrinogen levels, and with plasma viscosity (PMID:24178511)
• Novel APOA5-ZNF259 haplotype manifesting sex-dependent effects on elevation of the TG:HDL-C ratio as well as the increased risk for metabolic syndrome. (PMID:24618354)
• These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity. (PMID:24688311)
• Single nucleotide polymorphism zinc finger protein 259 gene is associated with hyperlipidaemia. (PMID:24780069)
• Significant linkage disequilibria were noted among ZNF259, BUD13 and MLXIPL SNPs and serum lipid levels. (PMID:24989072)
• ZNF259 variants were associated with elevated Metabolic Syndrome risk in a Han Chinese population from the Jilin province of Northeastern China (PMID:26118197)
• Single nucleotide polymorphisms (Rs964184, rs3317316, rs6589566) of ZNF259 protein did not increase the risk of CHD in the Chinese population. (PMID:26397108)
• When the inter-dependence between alleles was examined using conditional models, five loci on BUD13, ZNF259, and ApoA5 showed possible independent associations. (PMID:26634697)
• Results suggest that ZPR1 plays an important role in the etiology of type 2 diabetes mellitus, and this gene might be involved in abnormal glucose metabolism. (PMID:27411854)
• provide genetic and molecular evidence that a homozygous missense mutation in ZPR1 is associated with a rare and recognizable multisystem syndrome (PMID:29851065)
• Identification of a relationship between a genetic variant in CETP and ZNF259 gene with coronary artery disease (CAD) and CAD and lipid profile, respectively. Further investigation in a larger population may help to investigate the value of emerging marker as a risk stratification marker in CAD and its risk factors. (PMID:30902787)
• ZPR1 prevents R-loop accumulation, upregulates SMN2 expression and rescues spinal muscular atrophy. (PMID:31828288)
• The ZPR1 genotype predicts myocardial infarction in patients with familial hypercholesterolemia. (PMID:32807694)
• Implication between Genetic Variants from APOA5 and ZPR1 and NAFLD Severity in Patients with Hypertriglyceridemia. (PMID:33567543)
• Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study. (PMID:33986338)
• Zinc finger 259 gene polymorphisms in Egyptian patients with metabolic syndrome and its association with dyslipidemia. (PMID:38985417)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zpr1	ENSDARG00000043542
mus_musculus	Zpr1	ENSMUSG00000032078
rattus_norvegicus	Zpr1	ENSRNOG00000018481
drosophila_melanogaster	Zpr1	FBGN0030096
caenorhabditis_elegans		WBGENE00020999

Protein

Protein identifiers

Zinc finger protein ZPR1 — O75312 (reviewed: O75312)

Alternative names: Zinc finger protein 259

All UniProt accessions (6): O75312, F8WBC5, H7BZM7, H7BZS1, H7C0E5, H7C449

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus. It is involved in the positive regulation of cell cycle progression. Plays a role for the localization and accumulation of the survival motor neuron protein SMN1 in sub-nuclear bodies, including gems and Cajal bodies. Induces neuron differentiation and stimulates axonal growth and formation of growth cone in spinal cord motor neurons. Plays a role in the splicing of cellular pre-mRNAs. May be involved in H(2)O(2)-induced neuronal cell death.

Subunit / interactions. Component of an import snRNP complex composed of KPNB1, SNUPN, SMN1 and ZNF259. Interacts (via C-terminal region) with SMN1 (via C-terminal region); the interaction occurs after treatment with serum. Interacts with elongation factor 1-alpha EEF1A1; the interaction occurs in a epidermal growth factor (EGF)-dependent manner. Interacts (via zinc fingers) with EGFR (via C-terminal cytoplasmic kinase domain); the interaction is negatively regulated in response to epidermal growth factor (EGF) stimulation and the EGFR kinase activity. May also bind to the PDGFR receptor.

Subcellular location. Nucleus. Nucleolus. Gem. Cajal body. Cytoplasm. Perinuclear region. Cell projection. Axon. Growth cone.

Tissue specificity. Expressed in fibroblast; weakly expressed in fibroblast of spinal muscular atrophy (SMA) patients.

Disease relevance. Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (GKAF) [MIM:619321] An autosomal recessive disorder characterized by pre- and postnatal growth restriction with microcephaly, distinctive craniofacial features, congenital alopecia, hypoplastic kidneys with renal insufficiency, global developmental delay, severe congenital sensorineural hearing loss, hydrocephalus, genital hypoplasia, and early mortality. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ZPR1 family.

RefSeq proteins (2): NP_001304015, NP_003895* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004457	Znf_ZPR1	Domain
IPR040141	ZPR1	Family
IPR042451	ZPR1_A/B_dom	Homologous_superfamily
IPR042452	ZPR1_Znf1/2	Homologous_superfamily
IPR056180	ZPR1_jr_dom	Domain

Pfam: PF03367, PF22794

UniProt features (9 total): zinc finger region 2, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75312-F1	80.11	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 345 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_CELL_CYCLE_DNA_REPLICATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, MORF_HDAC2, GOBP_REGULATION_OF_MYELINATION

GO Biological Process (23): microtubule cytoskeleton organization (GO:0000226), inner cell mass cell proliferation (GO:0001833), trophectodermal cell proliferation (GO:0001834), DNA replication (GO:0006260), mRNA processing (GO:0006397), protein folding (GO:0006457), signal transduction (GO:0007165), RNA splicing (GO:0008380), positive regulation of gene expression (GO:0010628), spinal cord development (GO:0021510), Cajal body organization (GO:0030576), regulation of myelination (GO:0031641), positive regulation of RNA splicing (GO:0033120), DNA endoreduplication (GO:0042023), positive regulation of protein import into nucleus (GO:0042307), positive regulation of cell cycle (GO:0045787), positive regulation of growth (GO:0045927), axon development (GO:0061564), cellular response to epidermal growth factor stimulus (GO:0071364), apoptotic process involved in development (GO:1902742), pre-mRNA catabolic process (GO:1990261), negative regulation of motor neuron apoptotic process (GO:2000672), cell differentiation (GO:0030154)

GO Molecular Function (6): zinc ion binding (GO:0008270), receptor tyrosine kinase binding (GO:0030971), translation initiation factor binding (GO:0031369), protein folding chaperone (GO:0044183), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Cajal body (GO:0015030), axon (GO:0030424), growth cone (GO:0030426), neuronal cell body (GO:0043025), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471), Gemini of Cajal bodies (GO:0097504), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
blastocyst growth	2
cell population proliferation	2
RNA processing	2
cellular process	2
regulation of cellular process	2
anatomical structure development	2
nuclear lumen	2
cytoskeleton organization	1
microtubule-based process	1
DNA metabolic process	1
DNA biosynthetic process	1
mRNA metabolic process	1
protein maturation	1
cell communication	1
signaling	1
cellular response to stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
central nervous system development	1
nuclear body organization	1
myelination	1
regulation of nervous system development	1
RNA splicing	1
positive regulation of gene expression	1
regulation of RNA splicing	1
DNA replication initiation	1
cell cycle DNA replication	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
growth	1
regulation of growth	1
positive regulation of biological process	1

Protein interactions and networks

STRING

2460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZPR1	EGFR	P00533	915
ZPR1	BUD13	Q9BRD0	827
ZPR1	APOA5	Q6Q788	809
ZPR1	ZNF91	Q05481	765
ZPR1	ZFYVE1	Q9HBF4	765
ZPR1	ZFP37	Q9Y6Q3	736
ZPR1	ZIC4	Q8N9L1	733
ZPR1	RNF103	O00237	719
ZPR1	ZFY	P08048	702
ZPR1	CTCF	P49711	695
ZPR1	ZIC1	Q15915	684
ZPR1	K7ESF6	K7ESF6	670
ZPR1	ZNF44	P15621	670
ZPR1	ZNF569	Q5MCW4	670
ZPR1	ZNF501	Q96CX3	670
ZPR1	ZNF436	Q9C0F3	670
ZPR1	ZNF629	Q9UEG4	670

IntAct

21 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
ZBTB42	MID1	psi-mi:“MI:0914”(association)	0.530
EEF1A1	ZPR1	psi-mi:“MI:0914”(association)	0.530
ABHD5	ZPR1	psi-mi:“MI:0914”(association)	0.530
ZPR1	MPP3	psi-mi:“MI:0915”(physical association)	0.370
NEU4	AIP	psi-mi:“MI:0914”(association)	0.350
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.350
ABHD5	KDM4A	psi-mi:“MI:0914”(association)	0.350
HROB	ZPR1	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
rep	ARPC1B	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
CDK5RAP2	ZPR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (100): EEF1A1 (Co-fractionation), ZPR1 (Co-fractionation), ZPR1 (Co-fractionation), ZPR1 (Co-fractionation), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ZPR1 (Two-hybrid), ZPR1 (Affinity Capture-Western), ZPR1 (Proximity Label-MS)

ESM2 similar proteins: A7SJ66, A9CB27, D3ZVK1, O13724, O16999, O54820, O75312, O93257, P28340, P36776, P41250, P53303, P54358, P97283, Q08DS5, Q0IJ33, Q0V9S0, Q2TBX0, Q3B8G0, Q4R7D0, Q503I8, Q55E13, Q59HJ6, Q5F310, Q5R5N9, Q5RBL1, Q5RC82, Q5ZI25, Q5ZJM3, Q62384, Q6GNS3, Q6GQ76, Q6IR55, Q6P2Z6, Q7KUT2, Q803R5, Q8BLY2, Q8CGK3, Q924S5, Q965S0

Diamond homologs: A9CB27, O13724, O16999, O75312, P53303, Q2TBX0, Q55E13, Q57950, Q62384, Q9W379, O58960

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1077080	NM_003904.5(ZPR1):c.587T>C (p.Ile196Thr)	Pathogenic

SpliceAI

1841 predictions. Top by Δscore:

Variant	Effect	Δscore
11:116778921:A:AC	donor_gain	1.0000
11:116778922:C:CC	donor_gain	1.0000
11:116778952:ATAGC:A	donor_gain	1.0000
11:116778954:AGC:A	donor_gain	1.0000
11:116778983:AGCT:A	donor_gain	1.0000
11:116778984:G:C	donor_gain	1.0000
11:116779056:CATT:C	acceptor_gain	1.0000
11:116779058:TT:T	acceptor_gain	1.0000
11:116779060:C:CC	acceptor_gain	1.0000
11:116779767:TATA:T	donor_loss	1.0000
11:116779768:ATACC:A	donor_loss	1.0000
11:116779769:TAC:T	donor_loss	1.0000
11:116779770:A:T	donor_loss	1.0000
11:116779771:CCTGC:C	donor_loss	1.0000
11:116779834:TGAT:T	acceptor_gain	1.0000
11:116779835:GAT:G	acceptor_gain	1.0000
11:116779836:AT:A	acceptor_gain	1.0000
11:116779837:TC:T	acceptor_loss	1.0000
11:116779838:C:CA	acceptor_loss	1.0000
11:116779838:C:CC	acceptor_gain	1.0000
11:116779839:T:G	acceptor_loss	1.0000
11:116782153:CTTA:C	donor_loss	1.0000
11:116782156:A:AC	donor_gain	1.0000
11:116782156:ACCT:A	donor_loss	1.0000
11:116782157:C:CC	donor_gain	1.0000
11:116782157:CC:C	donor_loss	1.0000
11:116782240:GTCAC:G	acceptor_gain	1.0000
11:116782241:TCAC:T	acceptor_gain	1.0000
11:116782242:CAC:C	acceptor_gain	1.0000
11:116782242:CACC:C	acceptor_gain	1.0000

AlphaMissense

3044 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:116779781:A:C	S412R	0.998
11:116779781:A:T	S412R	0.998
11:116779783:T:G	S412R	0.998
11:116782958:G:C	F351L	0.998
11:116782958:G:T	F351L	0.998
11:116782960:A:G	F351L	0.998
11:116784416:C:G	A285P	0.998
11:116784421:A:T	I283N	0.998
11:116784435:A:C	F278L	0.998
11:116784435:A:T	F278L	0.998
11:116784437:A:G	F278L	0.998
11:116784900:A:G	C259R	0.998
11:116783614:T:A	K299N	0.997
11:116783614:T:G	K299N	0.997
11:116784890:C:G	C262S	0.997
11:116784891:A:T	C262S	0.997
11:116785610:A:C	S203R	0.997
11:116785610:A:T	S203R	0.997
11:116785612:T:G	S203R	0.997
11:116779008:G:T	R433S	0.996
11:116783018:G:C	C331W	0.996
11:116784406:C:G	C288S	0.996
11:116784407:A:G	C288R	0.996
11:116784407:A:T	C288S	0.996
11:116784421:A:C	I283S	0.996
11:116784436:A:G	F278S	0.996
11:116784891:A:G	C262R	0.996
11:116784899:C:G	C259S	0.996
11:116784900:A:T	C259S	0.996
11:116783534:A:T	L326H	0.995

dbSNP variants (sampled 300 via entrez): RS1000947519 (11:116774475 T>A), RS1000998195 (11:116774249 T>G), RS1001068835 (11:116776338 C>T), RS1001158680 (11:116781972 A>C), RS1001230791 (11:116781754 T>G), RS1001574327 (11:116774608 A>G), RS1001703534 (11:116777235 C>A), RS1001816678 (11:116788355 G>A,C,T), RS1002973209 (11:116773684 A>C,T), RS1003108698 (11:116773375 G>A), RS1003493976 (11:116776219 A>G), RS1003569523 (11:116777773 G>A), RS1003758326 (11:116789799 G>A,C,T), RS1003802141 (11:116786375 A>T), RS1003913191 (11:116779231 G>A)

Disease associations

OMIM: gene MIM:603901 | disease phenotypes: MIM:619321

GenCC curated gene-disease

Disease	Classification	Inheritance
growth restriction, hypoplastic kidneys, alopecia, and distinctive facies	Moderate	Autosomal recessive

Mondo (1): growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (MONDO:0859146)

Orphanet (0):

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000089	Renal hypoplasia
HP:0000185	Cleft soft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000293	Full cheeks
HP:0000319	Smooth philtrum
HP:0000444	Convex nasal ridge
HP:0000490	Deeply set eye
HP:0000556	Retinal dystrophy
HP:0000609	Optic nerve hypoplasia
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0001371	Flexion contracture
HP:0001397	Hepatic steatosis
HP:0001511	Intrauterine growth retardation
HP:0001596	Alopecia
HP:0001974	Increased total leukocyte count
HP:0002157	Azotemia
HP:0002566	Intestinal malrotation
HP:0002714	Downturned corners of mouth
HP:0002857	Genu valgum
HP:0003196	Short nose
HP:0004322	Short stature
HP:0007513	Generalized hypopigmentation
HP:0008278	Cerebellar cortical atrophy
HP:0008724	Hypoplasia of the ovary
HP:0008734	Decreased testicular size
HP:0011220	Prominent forehead

GWAS associations

121 associations (top):

Study	Trait	p-value
GCST000138_5	Triglycerides	2.000000e-17
GCST000671_2	Lipoprotein-associated phospholipase A2 activity and mass	4.000000e-08
GCST000805_4	HDL cholesterol	2.000000e-11
GCST000807_7	LDL cholesterol	2.000000e-06
GCST000809_11	Triglycerides	4.000000e-21
GCST000998_20	Coronary heart disease	1.000000e-17
GCST001003_3	Metabolic syndrome	2.000000e-09
GCST001004_2	Triglycerides-Blood Pressure (TG-BP)	3.000000e-09
GCST001005_7	HDL Cholesterol - Triglycerides (HDLC-TG)	2.000000e-14
GCST001006_7	Waist Circumference - Triglycerides (WC-TG)	1.000000e-16
GCST001007_11	Metabolic syndrome (bivariate traits)	1.000000e-08
GCST001142_1	Vitamin E levels	8.000000e-12
GCST001230_3	Triglycerides	2.000000e-86
GCST001273_7	Lipoprotein-associated phospholipase A2 activity and mass	8.000000e-11
GCST001436_9	Metabolic syndrome	3.000000e-31
GCST001450_3	Response to Vitamin E supplementation	3.000000e-12
GCST001450_5	Response to Vitamin E supplementation	4.000000e-07
GCST001762_665	Obesity-related traits	9.000000e-06
GCST001762_802	Obesity-related traits	3.000000e-08
GCST001905_3	Hypertriglyceridemia	5.000000e-35
GCST002289_10	Coronary artery disease	3.000000e-07
GCST002290_14	Coronary artery disease or large artery stroke	9.000000e-10
GCST002468_1	Triglycerides	6.000000e-33
GCST002653_1	Circulating phylloquinone levels	6.000000e-08
GCST002690_10	Very long-chain saturated fatty acid levels (fatty acid 20:0)	5.000000e-06
GCST003014_1	Postprandial triglyceride response to high fat diet meal	1.000000e-09
GCST003301_3	Triglycerides	3.000000e-83
GCST003302_1	Cholesterol, total	5.000000e-13
GCST003304_3	HDL cholesterol	8.000000e-10
GCST003364_2	Triglyceride levels	1.000000e-30

EFO canonical traits (36, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0000195	metabolic syndrome
EFO:0004618	vitamin K measurement
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0007681	triglyceride change measurement
EFO:0007684	response to high fat food intake
EFO:0004574	total cholesterol measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width
EFO:0007996	eosinophil percentage of granulocytes
EFO:0009188	Red cell distribution width
EFO:0007994	neutrophil percentage of granulocytes
EFO:0009925	Antithrombotic agent use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0007013	aspirin use measurement
EFO:0005105	lipid or lipoprotein measurement
EFO:0004729	vitamin measurement
EFO:0007898	alpha-tocopherol measurement
EFO:0010355	diacylglycerol 36:2 measurement
EFO:0010344	cholesteryl ester 18:1 measurement
EFO:0010342	cholesteryl ester 16:1 measurement
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0010414	triacylglycerol 52:2 measurement
EFO:0010347	cholesteryl ester 20:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs964184	APOA1, ZPR1	3	3.50	1	fenofibrate
rs2072560	APOA5, ZPR1		0.00	0
rs2266788	APOA5, ZPR1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, affects expression, decreases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	3
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
abrine	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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