ZNF141

Summary

ZNF141 (zinc finger protein 141, HGNC:12926) is a protein-coding gene on chromosome 4p16.3, encoding Zinc finger protein 141 (Q15928). May be involved in transcriptional regulation as a repressor.

The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A.

Source: NCBI Gene 7700 — RefSeq curated summary.

At a glance

• Gene–disease (curated): postaxial polydactyly type A (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 102 total — 1 pathogenic
• Phenotypes (HPO): 8
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_003441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12926
Approved symbol	ZNF141
Name	zinc finger protein 141
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	pHZ-44
Ensembl gene	ENSG00000131127
Ensembl biotype	protein_coding
OMIM	194648
Entrez	7700

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000240499, ENST00000366506, ENST00000503699, ENST00000505939, ENST00000512994, ENST00000579770, ENST00000885053, ENST00000885054

RefSeq mRNA: 5 — MANE Select: NM_003441 NM_001348277, NM_001348278, NM_001348279, NM_001348280, NM_003441

CCDS: CCDS33931, CCDS87195

Canonical transcript exons

ENST00000240499 — 4 exons

Exon	Start	End
ENSE00001669961	372664	384868
ENSE00002062523	337814	337986
ENSE00003471925	343782	343908
ENSE00003669896	344335	344430

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 86.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0834 / max 380.6294, expressed in 1619 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46487	14.6612	1604
46488	1.0076	511
46486	0.3460	173
46485	0.0686	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	86.67	gold quality
adrenal tissue	UBERON:0018303	86.62	gold quality
tendon	UBERON:0000043	85.45	gold quality
tendon of biceps brachii	UBERON:0008188	84.65	gold quality
lower esophagus mucosa	UBERON:0035834	84.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.94	gold quality
colonic epithelium	UBERON:0000397	83.54	gold quality
cerebellar hemisphere	UBERON:0002245	82.77	gold quality
cerebellar cortex	UBERON:0002129	82.59	gold quality
sural nerve	UBERON:0015488	82.34	gold quality
left ovary	UBERON:0002119	81.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.34	gold quality
cerebellum	UBERON:0002037	80.40	gold quality
right ovary	UBERON:0002118	80.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.91	gold quality
buccal mucosa cell	CL:0002336	79.76	gold quality
cortical plate	UBERON:0005343	79.26	gold quality
ovary	UBERON:0000992	78.80	gold quality
ventricular zone	UBERON:0003053	78.78	gold quality
adenohypophysis	UBERON:0002196	78.53	gold quality
right uterine tube	UBERON:0001302	77.48	gold quality
ganglionic eminence	UBERON:0004023	77.43	gold quality
pituitary gland	UBERON:0000007	77.42	gold quality
primary visual cortex	UBERON:0002436	77.36	gold quality
caudate nucleus	UBERON:0001873	77.33	gold quality
apex of heart	UBERON:0002098	77.02	gold quality
nucleus accumbens	UBERON:0001882	76.99	gold quality
putamen	UBERON:0001874	76.43	gold quality
granulocyte	CL:0000094	76.27	gold quality
mucosa of transverse colon	UBERON:0004991	76.22	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

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 2)

• This study revealed involvement of a zinc finger gene ZNF141 in causing autosomal recessive PAP type A, which may open up interesting perspectives into the function of this protein in limb development. (PMID:23160277)
• To date, at least ten loci and four non-syndromic polydactyly-causing genes, including the GLI3 gene, the ZNF141 gene, the MIPOL1 gene and the PITX1 gene, have been identified. (Review) (PMID:26515020)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 141 — Q15928 (reviewed: Q15928)

All UniProt accessions (3): Q15928, D6RB60, D6RIY0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation as a repressor. Plays a role in limb development.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously low expression.

Disease relevance. Polydactyly, postaxial A6 (PAPA6) [MIM:615226] A condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (3): NP_001335206, NP_001335207, NP_003432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF01352, PF13912

UniProt features (17 total): zinc finger region 11, sequence variant 4, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15928-F1	70.46	0.23

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins

MSigDB gene sets: 121 (showing top): MORF_RAD51L3, GOBP_APPENDAGE_DEVELOPMENT, MORF_PRKCA, chr4p16, MODULE_123, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, MORF_THPO, KANG_IMMORTALIZED_BY_TERT_DN, MORF_ATF2, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MORF_IL16, MORF_DMPK, MORF_ERCC4, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366), anatomical structure morphogenesis (GO:0009653), limb morphogenesis (GO:0035108)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
developmental process	1
anatomical structure development	1
appendage morphogenesis	1
limb development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF141	IQCE	Q6IPM2	706
ZNF141	KIAA0825	Q8IV33	583
ZNF141	CIBAR1	A1XBS5	576
ZNF141	MIPOL1	Q8TD10	515
ZNF141	PIGG	Q5H8A4	431
ZNF141	LMBR1	Q8WVP7	400
ZNF141	PITX1	P78337	384
ZNF141	STKLD1	Q8NE28	371
ZNF141	LEMD3	Q9Y2U8	371
ZNF141	CREG2	Q8IUH2	367
ZNF141	WIPF1	O43516	356
ZNF141	SREK1IP1	Q8N9Q2	356
ZNF141	P2RX1	P51575	342
ZNF141	SFXN3	Q9BWM7	329
ZNF141	MFSD6L	Q8IWD5	325

IntAct

0 interactions, top by confidence:

BioGRID (3): ZNF141 (Affinity Capture-MS), ZNF141 (Proximity Label-MS), ZNF141 (Affinity Capture-RNA)

ESM2 similar proteins: A2RRD8, A6NHJ4, B4DX44, O75346, P10077, P10755, P15621, P16372, P16373, P51786, P52737, P85977, Q0VGE8, Q14588, Q147U1, Q15928, Q15973, Q2M3X9, Q3KNS6, Q3MIS6, Q494X3, Q5HY98, Q5RBQ3, Q5REK1, Q5VIY5, Q60585, Q61751, Q6GQR8, Q7L2R6, Q7TSH9, Q8IYX0, Q8N782, Q8N823, Q8N988, Q8N9F8, Q8NA42, Q8NCK3, Q8NDP4, Q8NEP9, Q8TC21

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	16
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062749	GRCh37/hg19 4p16.3(chr4:68345-463962)x1	Pathogenic

SpliceAI

1145 predictions. Top by Δscore:

Variant	Effect	Δscore
4:343905:CTGGG:C	donor_loss	1.0000
4:343906:TGGG:T	donor_loss	1.0000
4:343907:GG:G	donor_gain	1.0000
4:343908:GG:G	donor_gain	1.0000
4:343909:GTG:G	donor_loss	1.0000
4:343910:T:A	donor_loss	1.0000
4:372663:GCTAT:G	acceptor_gain	1.0000
4:339595:A:T	donor_gain	0.9900
4:342382:T:TA	donor_gain	0.9900
4:342383:G:GA	donor_gain	0.9900
4:342398:A:AG	donor_gain	0.9900
4:342399:G:GG	donor_gain	0.9900
4:342955:GC:G	donor_gain	0.9900
4:343909:G:GG	donor_gain	0.9900
4:343911:G:GG	donor_loss	0.9900
4:343914:GA:G	donor_gain	0.9900
4:344324:A:G	acceptor_gain	0.9900
4:344332:CAGG:C	acceptor_loss	0.9900
4:344334:G:GT	acceptor_loss	0.9900
4:344334:GGT:G	acceptor_gain	0.9900
4:344427:CCAG:C	donor_loss	0.9900
4:344429:AGG:A	donor_loss	0.9900
4:344430:GG:G	donor_loss	0.9900
4:344431:G:A	donor_loss	0.9900
4:344432:TAGG:T	donor_loss	0.9900
4:372659:TTCA:T	acceptor_loss	0.9900
4:372660:TCAGC:T	acceptor_loss	0.9900
4:372661:CA:C	acceptor_loss	0.9900
4:372662:A:AG	acceptor_gain	0.9900
4:372662:AGC:A	acceptor_loss	0.9900

AlphaMissense

3172 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:373563:T:C	F376L	0.995
4:373565:T:A	F376L	0.995
4:373565:T:G	F376L	0.995
4:373395:T:C	F320L	0.992
4:373397:T:A	F320L	0.992
4:373397:T:G	F320L	0.992
4:373479:T:C	F348L	0.992
4:373481:T:A	F348L	0.992
4:373481:T:G	F348L	0.992
4:373647:T:C	F404L	0.990
4:373649:T:A	F404L	0.990
4:373649:T:G	F404L	0.990
4:373227:T:C	F264L	0.986
4:373229:T:A	F264L	0.986
4:373229:T:G	F264L	0.986
4:373654:G:C	R406P	0.981
4:373731:T:C	F432L	0.981
4:373733:T:A	F432L	0.981
4:373733:T:G	F432L	0.981
4:373592:T:A	H385Q	0.977
4:373592:T:G	H385Q	0.977
4:373508:T:A	H357Q	0.976
4:373508:T:G	H357Q	0.976
4:373815:T:C	F460L	0.976
4:373817:T:A	F460L	0.976
4:373817:T:G	F460L	0.976
4:373582:T:C	L382P	0.975
4:373436:T:A	H333Q	0.974
4:373436:T:G	H333Q	0.974
4:373604:T:A	H389Q	0.973

dbSNP variants (sampled 300 via entrez): RS1000004977 (4:341508 A>G), RS1000010522 (4:350393 T>C), RS1000037379 (4:374744 A>G), RS1000164521 (4:377395 C>T), RS1000178561 (4:336759 G>A), RS1000294540 (4:336964 C>T), RS1000420504 (4:371616 T>C), RS1000524719 (4:341894 T>G), RS1000648196 (4:366360 G>A), RS1000710169 (4:359749 C>T), RS1000892984 (4:354606 T>C), RS1000936844 (4:366012 C>G), RS10010884 (4:378213 G>A,C), RS1001102423 (4:381306 C>G), RS1001129671 (4:340618 T>G)

Disease associations

OMIM: gene MIM:194648 | disease phenotypes: MIM:615226

GenCC curated gene-disease

Disease	Classification	Inheritance
postaxial polydactyly type A	Supportive	Autosomal recessive
polydactyly, postaxial, type A6	Limited	Autosomal recessive

Mondo (2): polydactyly, postaxial, type A6 (MONDO:0014090), postaxial polydactyly type A (MONDO:0019673)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000971	Abnormal sweat gland morphology
HP:0001162	Postaxial hand polydactyly
HP:0001597	Abnormal nail morphology
HP:0001830	Postaxial foot polydactyly
HP:0003577	Congenital onset
HP:0006482	Abnormal dental morphology
HP:0009374	Broad phalanges of the 5th finger

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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Arbutin	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Clorgyline	increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vitamin E	decreases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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