ZNF541

Summary

ZNF541 (zinc finger protein 541, HGNC:25294) is a protein-coding gene on chromosome 19q13.33, encoding Zinc finger protein 541 (Q9H0D2). Transcription regulator which is essential for male fertility and for the completion of meiotic prophase in spermatocytes.

Predicted to enable transcription corepressor activity. Predicted to be involved in male meiotic nuclear division and regulation of DNA-templated transcription. Predicted to be located in nucleus. Predicted to be part of histone deacetylase complex and transcription regulator complex.

Source: NCBI Gene 84215 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_001277075

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25294
Approved symbol	ZNF541
Name	zinc finger protein 541
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434I1930
Ensembl gene	ENSG00000118156
Ensembl biotype	protein_coding
OMIM	619942
Entrez	84215

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000263351, ENST00000391901, ENST00000487275, ENST00000595558

RefSeq mRNA: 1 — MANE Select: NM_001277075 NM_001277075

CCDS: CCDS46133

Canonical transcript exons

ENST00000391901 — 17 exons

Exon	Start	End
ENSE00000930221	47521479	47521654
ENSE00000930223	47528950	47529038
ENSE00000930224	47529577	47529652
ENSE00000952994	47544126	47545980
ENSE00000952995	47540893	47540951
ENSE00000952998	47538142	47538439
ENSE00000953000	47532128	47532270
ENSE00000953001	47531642	47531745
ENSE00000953002	47521854	47521994
ENSE00001510044	47520690	47521377
ENSE00001510048	47549245	47549485
ENSE00001510049	47555550	47555954
ENSE00003606546	47539705	47539878
ENSE00003636333	47532909	47532972
ENSE00003638438	47540176	47540335
ENSE00003926683	47573083	47573148
ENSE00003933466	47571896	47572042

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 83.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0639 / max 31.5759, expressed in 13 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181787	0.0361	11
181786	0.0278	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	83.91	gold quality
right testis	UBERON:0004534	83.77	gold quality
testis	UBERON:0000473	82.04	gold quality
sperm	CL:0000019	80.97	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.79	gold quality
adrenal tissue	UBERON:0018303	74.11	gold quality
left adrenal gland cortex	UBERON:0035825	73.97	gold quality
pancreatic ductal cell	CL:0002079	72.86	silver quality
adrenal cortex	UBERON:0001235	72.50	gold quality
right adrenal gland cortex	UBERON:0035827	72.18	gold quality
left adrenal gland	UBERON:0001234	72.02	gold quality
right adrenal gland	UBERON:0001233	71.73	gold quality
adult organism	UBERON:0007023	70.29	gold quality
adrenal gland	UBERON:0002369	70.21	gold quality
secondary oocyte	CL:0000655	69.29	silver quality
kidney epithelium	UBERON:0004819	68.67	gold quality
endothelial cell	CL:0000115	68.21	silver quality
tibialis anterior	UBERON:0001385	67.76	silver quality
left ovary	UBERON:0002119	66.86	gold quality
calcaneal tendon	UBERON:0003701	66.44	gold quality
deltoid	UBERON:0001476	65.10	silver quality
apex of heart	UBERON:0002098	63.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.87	gold quality
left ventricle myocardium	UBERON:0006566	63.87	gold quality
ovary	UBERON:0000992	63.66	gold quality
tendon	UBERON:0000043	63.58	gold quality
right ovary	UBERON:0002118	61.88	gold quality
ileal mucosa	UBERON:0000331	61.55	silver quality
myocardium	UBERON:0002349	60.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf541	ENSDARG00000052188
mus_musculus	Zfp541	ENSMUSG00000078796
rattus_norvegicus	Zfp541	ENSRNOG00000021800
drosophila_melanogaster	CG16779	FBGN0037698
caenorhabditis_elegans		WBGENE00005006
caenorhabditis_elegans		WBGENE00009224
caenorhabditis_elegans		WBGENE00010012
caenorhabditis_elegans		WBGENE00013632
caenorhabditis_elegans	rcor-1	WBGENE00022278

Paralogs (5): RCOR1 (ENSG00000089902), RCOR3 (ENSG00000117625), TRERF1 (ENSG00000124496), MIDEAS (ENSG00000156030), RCOR2 (ENSG00000167771)

Protein

Protein identifiers

Zinc finger protein 541 — Q9H0D2 (reviewed: Q9H0D2)

All UniProt accessions (3): Q9H0D2, H7BXG6, M0R167

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator which is essential for male fertility and for the completion of meiotic prophase in spermatocytes. Regulates progression of the pachytene stage of meiotic prophase by activating the expression of genes involved in meiosis during spermatogenesis. Maintains the repression of pre-pachytene transcriptional programs, including meiotic double-strand breaks (DSB) formation genes in pachytene spermatocytes and suppresses aberrant DSB formation after mid-pachytene, thus ensuring meiosis progression.

Subunit / interactions. Interacts with DNTTIP1. Identified in a complex with KCDT19, HDAC1 and HSPA2. Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2. Identified in a complex with HDAC1, HDAC2, DNTTIP1 and KCTD19.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0D2-3	3	yes
Q9H0D2-2	2

RefSeq proteins (1): NP_001264004* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000949	ELM2_dom	Domain
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR017884	SANT_dom	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051066	Trans_reg/Corepressor	Family

Pfam: PF00096, PF01448, PF13912

UniProt features (30 total): region of interest 8, compositionally biased region 8, zinc finger region 5, sequence variant 4, domain 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0D2-F1	45.27	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_ORGANELLE_FISSION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_MEIOTIC_CELL_CYCLE, RAAGNYNNCTTY_UNKNOWN, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, RNCTGNYNRNCTGNY_UNKNOWN, GOBP_CELL_CYCLE_PROCESS, GOCC_HISTONE_DEACETYLASE_COMPLEX, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, AR_Q6, GOBP_MALE_MEIOTIC_NUCLEAR_DIVISION, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY

GO Biological Process (8): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), male meiotic nuclear division (GO:0007140), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), meiotic cell cycle (GO:0051321)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
male gamete generation	2
meiotic nuclear division	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
meiotic cell cycle	1
developmental process involved in reproduction	1
cellular developmental process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
transition metal ion binding	1
binding	1
cation binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF541	DNTTIP1	Q9H147	711
ZNF541	RPS6KL1	Q9Y6S9	667
ZNF541	M0QYG6	M0QYG6	581
ZNF541	CCDC51	Q96ER9	534
ZNF541	ARHGAP23	Q9P227	528
ZNF541	ZNF710	Q8N1W2	512
ZNF541	SNRPN	P14648	504
ZNF541	POLD1	P28340	491
ZNF541	IFT140	Q96RY7	438
ZNF541	ADPRHL1	Q8NDY3	437
ZNF541	GOLGA6L6	A8MZA4	418
ZNF541	ADK	P55263	404
ZNF541	ADGRD2	Q7Z7M1	400
ZNF541	ODF4	Q2M2E3	394
ZNF541	ADAMTS16	Q8TE57	381

IntAct

8 interactions, top by confidence:

A	B	Type	Score
AJUBA	ZNF541	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	ZNF541	psi-mi:“MI:0915”(physical association)	0.560
MYC		psi-mi:“MI:0914”(association)	0.350
ZNF541	AJUBA	psi-mi:“MI:0915”(physical association)	0.000
ZNF541	TRIP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): ZNF541 (Two-hybrid), AJUBA (Two-hybrid), ZNF541 (Cross-Linking-MS (XL-MS)), PFN1 (Cross-Linking-MS (XL-MS)), HSP90AA1 (Cross-Linking-MS (XL-MS)), HSP90AB1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: A5PJX4, O75376, P25357, Q0GGX2, Q4KKX4, Q4R2Z8, Q55DP9, Q59E36, Q5FWT8, Q60974, Q6NRZ0, Q6P116, Q8C796, Q8CFE3, Q8IZ40, Q8QG78, Q90WN5, Q9H0D2, Q9H4R4, Q9P2K3, Q9UKL0, Q9WU42, Q9WUB5, Q9Y618, Q3U3N0, Q5REE1, Q5UAK0, Q5ZJ40, Q5ZKT9, Q6PGA0, Q6PJG2, Q7T105, Q8BXJ2, Q8N108, Q8N344, Q96PN7, Q3UHF3, Q4R3R9, Q62599, Q7Z3K6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2603 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47521374:CACC:C	acceptor_gain	1.0000
19:47521376:CC:C	acceptor_gain	1.0000
19:47521377:CC:C	acceptor_gain	1.0000
19:47521378:C:CA	acceptor_loss	1.0000
19:47521378:C:CC	acceptor_gain	1.0000
19:47521379:T:G	acceptor_loss	1.0000
19:47521478:CCTT:C	donor_gain	1.0000
19:47521523:T:TA	donor_gain	1.0000
19:47521524:C:A	donor_gain	1.0000
19:47531746:C:CC	acceptor_gain	1.0000
19:47531763:A:AC	acceptor_gain	1.0000
19:47531763:A:C	acceptor_gain	1.0000
19:47532907:A:AC	donor_gain	1.0000
19:47532908:C:CC	donor_gain	1.0000
19:47532908:CGG:C	donor_gain	1.0000
19:47539717:C:CA	donor_gain	1.0000
19:47540191:C:A	donor_gain	1.0000
19:47540336:C:CC	acceptor_gain	1.0000
19:47540345:A:C	acceptor_gain	1.0000
19:47549236:C:CA	donor_gain	1.0000
19:47549243:A:AC	donor_gain	1.0000
19:47549244:C:CC	donor_gain	1.0000
19:47549262:AAAGG:A	donor_gain	1.0000
19:47549294:T:TA	donor_gain	1.0000
19:47549299:T:A	donor_gain	1.0000
19:47555545:CTCA:C	donor_loss	1.0000
19:47555546:TCA:T	donor_loss	1.0000
19:47555547:CAC:C	donor_loss	1.0000
19:47555549:C:CA	donor_loss	1.0000
19:47521378:C:T	acceptor_gain	0.9900

AlphaMissense

8777 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47545973:G:C	H186D	0.999
19:47549262:A:C	F177L	0.999
19:47549262:A:T	F177L	0.999
19:47549264:A:G	F177L	0.999
19:47549285:A:G	C170R	0.999
19:47549346:G:C	F149L	0.999
19:47549346:G:T	F149L	0.999
19:47549348:A:G	F149L	0.999
19:47549369:A:G	C142R	0.999
19:47545971:G:C	H186Q	0.998
19:47545971:G:T	H186Q	0.998
19:47549245:A:G	L183P	0.998
19:47549261:T:C	K178E	0.998
19:47549263:A:G	F177S	0.998
19:47549274:G:C	C173W	0.998
19:47549275:C:T	C173Y	0.998
19:47549276:A:G	C173R	0.998
19:47549307:G:C	H162Q	0.998
19:47549307:G:T	H162Q	0.998
19:47549319:G:C	H158Q	0.998
19:47549319:G:T	H158Q	0.998
19:47549358:G:C	C145W	0.998
19:47549359:C:T	C145Y	0.998
19:47549360:A:G	C145R	0.998
19:47549367:G:C	C142W	0.998
19:47521371:A:C	F1298L	0.997
19:47521371:A:T	F1298L	0.997
19:47521373:A:G	F1298L	0.997
19:47545891:A:G	L213P	0.997
19:47549259:C:A	K178N	0.997

dbSNP variants (sampled 300 via entrez): RS1000016070 (19:47542841 A>G), RS1000097108 (19:47547629 G>C), RS1000200464 (19:47558358 G>T), RS1000258500 (19:47552077 C>T), RS1000275382 (19:47561346 G>A), RS1000355405 (19:47521914 G>A), RS1000394063 (19:47523730 A>G), RS1000439402 (19:47545744 G>A), RS1000459123 (19:47567011 G>A), RS1000463337 (19:47546053 C>T), RS1000739085 (19:47546911 G>A), RS1000742925 (19:47555387 G>A), RS1000768587 (19:47566012 A>G), RS1000795433 (19:47551069 G>T), RS1000806809 (19:47522621 C>T)

Disease associations

OMIM: gene MIM:619942 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Limited	Autosomal recessive

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_65	Bipolar disorder	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, decreases expression, decreases methylation	3
perfluorooctanoic acid	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
bleomycetin	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Phenobarbital	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	affects expression	1

Clinical trials (associated diseases)

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