ZNF205

Summary

ZNF205 (zinc finger protein 205, HGNC:12996) is a protein-coding gene on chromosome 16p13.3, encoding Transcriptional repressor RHIT (O95201). Transcriptional repressor involved in regulating MPV17L expression.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of hydrogen peroxide biosynthetic process; and positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Predicted to be located in mitochondrion and nucleus.

Source: NCBI Gene 7755 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_001042428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12996
Approved symbol	ZNF205
Name	zinc finger protein 205
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Zfp13
Ensembl gene	ENSG00000122386
Ensembl biotype	protein_coding
OMIM	603436
Entrez	7755

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000219091, ENST00000382192, ENST00000414351, ENST00000444510, ENST00000570935, ENST00000620094, ENST00000871314, ENST00000871315, ENST00000871316, ENST00000871317, ENST00000871318, ENST00000871319, ENST00000871320, ENST00000922265, ENST00000922266

RefSeq mRNA: 3 — MANE Select: NM_001042428 NM_001042428, NM_001278158, NM_003456

CCDS: CCDS10494

Canonical transcript exons

ENST00000219091 — 7 exons

Exon	Start	End
ENSE00000665990	3115829	3115920
ENSE00000666011	3116427	3116547
ENSE00000666021	3118905	3119015
ENSE00001293954	3119256	3120517
ENSE00001350470	3113417	3113487
ENSE00001491197	3115355	3115568
ENSE00001942893	3112586	3112682

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5508 / max 70.6191, expressed in 1577 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152396	7.5508	1577

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.91	gold quality
vena cava	UBERON:0004087	90.80	gold quality
parotid gland	UBERON:0001831	90.58	gold quality
cervix squamous epithelium	UBERON:0006922	90.37	silver quality
medial globus pallidus	UBERON:0002477	90.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.54	gold quality
globus pallidus	UBERON:0001875	88.58	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	87.53	gold quality
triceps brachii	UBERON:0001509	87.13	gold quality
body of tongue	UBERON:0011876	86.72	gold quality
gluteal muscle	UBERON:0002000	86.40	silver quality
apex of heart	UBERON:0002098	85.46	gold quality
cortical plate	UBERON:0005343	84.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.27	gold quality
pylorus	UBERON:0001166	84.03	gold quality
tongue	UBERON:0001723	83.94	gold quality
cardia of stomach	UBERON:0001162	83.72	gold quality
upper arm skin	UBERON:0004263	83.57	silver quality
nipple	UBERON:0002030	83.31	gold quality
lower esophagus mucosa	UBERON:0035834	83.13	gold quality
ganglionic eminence	UBERON:0004023	83.03	gold quality
pons	UBERON:0000988	82.98	gold quality
inferior olivary complex	UBERON:0002127	82.98	gold quality
pharyngeal mucosa	UBERON:0000355	82.70	gold quality
tongue squamous epithelium	UBERON:0006919	82.47	silver quality
inferior vagus X ganglion	UBERON:0005363	82.30	gold quality
subthalamic nucleus	UBERON:0001906	82.27	silver quality
ventral tegmental area	UBERON:0002691	82.20	gold quality
saphenous vein	UBERON:0007318	82.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
MPV17	Repression
MPV17L	Unknown

Upstream regulators (CollecTRI, top): FOXP3, GABPA, STAT1

miRNA regulators (miRDB)

4 targeting ZNF205, 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-185-3P	99.95	67.01	1743
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-6872-3P	97.08	66.99	750

Literature-anchored findings (GeneRIF, showing 2)

• that knockdown of RhitH or overexpression of M-LPH reduces the generation of intracellular H(2)O(2) and loss of mitochondrial membrane potential caused by an inhibitor of the respiratory chain, antimycin A (PMID:22306510)
• ZNF205 positively regulates RLR antiviral signaling by targeting RIG-I. (PMID:37580950)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp13	ENSMUSG00000062012
rattus_norvegicus	Zfp13	ENSRNOG00000003455

Paralogs (30): ZNF263 (ENSG00000006194), ZNF213 (ENSG00000085644), ZNF500 (ENSG00000103199), ZKSCAN1 (ENSG00000106261), ZSCAN9 (ENSG00000137185), PGBD1 (ENSG00000137338), ZNF215 (ENSG00000149054), ZSCAN12 (ENSG00000158691), ZNF394 (ENSG00000160908), ZNF75A (ENSG00000162086), ZSCAN21 (ENSG00000166529), ZNF232 (ENSG00000167840), ZNF24 (ENSG00000172466), ZNF449 (ENSG00000173275), ZSCAN4 (ENSG00000180532), ZSCAN22 (ENSG00000182318), ZNF75D (ENSG00000186376), ZNF396 (ENSG00000186496), ZNF397 (ENSG00000186812), ZSCAN30 (ENSG00000186814), ZKSCAN4 (ENSG00000187626), ZSCAN23 (ENSG00000187987), ZKSCAN3 (ENSG00000189298), ZSCAN16 (ENSG00000196812), ZSCAN25 (ENSG00000197037), ZSCAN26 (ENSG00000197062), ZNF165 (ENSG00000197279), ZKSCAN8 (ENSG00000198315), ZSCAN31 (ENSG00000235109), ZNF853 (ENSG00000236609)

Protein

Protein identifiers

Transcriptional repressor RHIT — O95201 (reviewed: O95201)

Alternative names: Repressor of heat-inducible transcription, Zinc finger protein 205, Zinc finger protein 210

All UniProt accessions (4): C9JEY6, C9JS60, O95201, I3L417

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor involved in regulating MPV17L expression. By regulating MPV17L expression, contributes to the regulation of genes involved in H(2)O(2) metabolism and the mitochondrial apoptotic cascade.

Subcellular location. Nucleus.

Tissue specificity. Expressed in heart, skeletal muscle, pancreas and brain. Weakly expressed in placenta, lung, liver, kidney and thymus.

Domain organisation. The KRAB domain is required for transcriptional repression.

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

RefSeq proteins (3): NP_001035893, NP_001265087, NP_003447 (=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
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352

UniProt features (20 total): zinc finger region 8, region of interest 3, compositionally biased region 3, sequence variant 2, chain 1, domain 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95201-F1	63.49	0.21

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 (2): 292, 219

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 114 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, HUMMERICH_BENIGN_SKIN_TUMOR_UP, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, RYTTCCTG_ETS2_B, GOBP_REGULATION_OF_MITOCHONDRIAL_OUTER_MEMBRANE_PERMEABILIZATION_INVOLVED_IN_APOPTOTIC_SIGNALING_PATHWAY, ELK1_01

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of hydrogen peroxide biosynthetic process (GO:0010729), positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901030), positive regulation of biosynthetic process (GO:0009891)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
regulation of hydrogen peroxide biosynthetic process	1
hydrogen peroxide biosynthetic process	1
positive regulation of reactive oxygen species biosynthetic process	1
positive regulation of organelle organization	1
positive regulation of mitochondrial membrane permeability	1
positive regulation of transport	1
mitochondrial outer membrane permeabilization	1
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1
biosynthetic process	1
regulation of biosynthetic process	1
positive regulation of metabolic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
transcription cis-regulatory region binding	1
nucleic acid binding	1
binding	1
cation binding	1
cytoplasm	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF205	OR1F1	O43749	887
ZNF205	MEFV	O15553	717
ZNF205	COQ9	O75208	540
ZNF205	NEU2	Q9Y3R4	520
ZNF205	NAT9	Q9BTE0	518
ZNF205	SVOPL	Q8N434	502
ZNF205	GCGR	P47871	474
ZNF205	PAFAH1B3	Q15102	444
ZNF205	CCNP	Q9H8S5	439
ZNF205	MPV17L	Q2QL34	419
ZNF205	BST2	Q10589	408
ZNF205	EP300	Q09472	398
ZNF205	SEC61G	P38384	398
ZNF205	PLA2G1B	P04054	359
ZNF205	RAB15	P59190	359

IntAct

29 interactions, top by confidence:

A	B	Type	Score
ZNF205	TNS2	psi-mi:“MI:0915”(physical association)	0.560
ZNF205	TSGA10	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ZNF205	psi-mi:“MI:0915”(physical association)	0.560
ZNF205	PICK1	psi-mi:“MI:0915”(physical association)	0.560
ZNF205	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
UBQLN4	ZNF205	psi-mi:“MI:0915”(physical association)	0.510
ZNF205	C8orf33	psi-mi:“MI:0915”(physical association)	0.370
ZNF205	CDC37	psi-mi:“MI:0915”(physical association)	0.370
HDAC6	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
ZNF205	ILK	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
MEST	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
WT1	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
ZNF205	CCDC85B	psi-mi:“MI:0915”(physical association)	0.370
ZNF205	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.370
TRAF2	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
MDFI	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
TNS2	ZNF205	psi-mi:“MI:0915”(physical association)	0.000
ZNF205	TSGA10	psi-mi:“MI:0915”(physical association)	0.000
ZNF205	GOLGA6L9	psi-mi:“MI:0915”(physical association)	0.000
ZNF205	PICK1	psi-mi:“MI:0915”(physical association)	0.000
ZNF205	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
ZNF205	UBQLN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): CCDC85B (Two-hybrid), CALCOCO2 (Two-hybrid), ZNF205 (Two-hybrid), ZNF205 (Two-hybrid), ZNF205 (Affinity Capture-MS), ZNF205 (Affinity Capture-MS), ZNF205 (Affinity Capture-RNA), ZNF205 (Two-hybrid), ZNF205 (Two-hybrid), TSGA10 (Two-hybrid), UBQLN2 (Two-hybrid), GOLGA6L9 (Two-hybrid), ZNF205 (Affinity Capture-RNA), ZNF205 (Two-hybrid), ZNF205 (Two-hybrid)

ESM2 similar proteins: A1YGK1, A2T7E6, A4D1S0, A9YTQ3, B1WBS3, I7HJS4, O43593, O43918, O60304, O75593, O95201, P0C6A0, P0C7X2, P97609, Q2MHN3, Q3B7M4, Q3SY56, Q3U133, Q58DK7, Q5JPB2, Q5SXI5, Q5T619, Q61645, Q6KAU7, Q6NUN9, Q6ZMS7, Q76NI1, Q7Z6P3, Q8BZ34, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8NBB4, Q8NDX1, Q8NHY3, Q91X45, Q96PX9, Q99558

Diamond homologs: A2T736, A3KN32, A3KN36, A6NFI3, A6NP11, A6QPT6, A8MT65, B2RXC5, B4DU55, B4DXR9, O14978, O43296, O60765, O95125, O95201, P0CB33, P0DPD5, P10754, P15622, P17036, P17098, P21506, P51508, P51815, Q02975, Q08DG8, Q08ER8, Q13106, Q13360, Q15776, Q15973, Q29RZ4, Q32M78, Q3SXZ3, Q4R8H9, Q4V8E9, Q571J5, Q58DK7, Q5CZA5, Q5FWF6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1569 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3115487:G:GT	donor_gain	1.0000
16:3115827:A:AG	acceptor_gain	1.0000
16:3115828:G:GG	acceptor_gain	1.0000
16:3115828:GCC:G	acceptor_gain	1.0000
16:3116514:G:T	donor_gain	1.0000
16:3116544:CTGG:C	donor_gain	1.0000
16:3116545:TGG:T	donor_gain	1.0000
16:3116546:GG:G	donor_gain	1.0000
16:3116546:GGG:G	donor_gain	1.0000
16:3116547:GG:G	donor_gain	1.0000
16:3116548:G:GG	donor_gain	1.0000
16:3116548:GT:G	donor_loss	1.0000
16:3116549:T:G	donor_loss	1.0000
16:3113485:G:GT	donor_gain	0.9900
16:3115353:AG:A	acceptor_gain	0.9900
16:3115354:GG:G	acceptor_gain	0.9900
16:3115490:G:GT	donor_gain	0.9900
16:3115533:GCTC:G	donor_gain	0.9900
16:3115823:CCACA:C	acceptor_loss	0.9900
16:3115824:CACA:C	acceptor_loss	0.9900
16:3115825:ACAG:A	acceptor_loss	0.9900
16:3115826:CA:C	acceptor_loss	0.9900
16:3115828:GC:G	acceptor_gain	0.9900
16:3115828:GCCC:G	acceptor_gain	0.9900
16:3115828:GCCCT:G	acceptor_gain	0.9900
16:3116543:ACTGG:A	donor_gain	0.9900
16:3119251:TCCAG:T	acceptor_loss	0.9900
16:3119252:CCAG:C	acceptor_loss	0.9900
16:3119254:A:AG	acceptor_gain	0.9900
16:3119255:G:GG	acceptor_gain	0.9900

AlphaMissense

3614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3119777:T:C	F373L	1.000
16:3119779:C:A	F373L	1.000
16:3119779:C:G	F373L	1.000
16:3119861:T:C	F401L	1.000
16:3119863:C:A	F401L	1.000
16:3119863:C:G	F401L	1.000
16:3119945:T:C	F429L	1.000
16:3119947:C:A	F429L	1.000
16:3119947:C:G	F429L	1.000
16:3120029:T:C	F457L	1.000
16:3120031:C:A	F457L	1.000
16:3120031:C:G	F457L	1.000
16:3120048:T:C	L463P	1.000
16:3120063:G:C	R468P	1.000
16:3120113:T:C	F485L	1.000
16:3120114:T:C	F485S	1.000
16:3120115:C:A	F485L	1.000
16:3120115:C:G	F485L	1.000
16:3120132:T:C	L491P	1.000
16:3120197:T:C	F513L	1.000
16:3120198:T:C	F513S	1.000
16:3120199:C:A	F513L	1.000
16:3120199:C:G	F513L	1.000
16:3119609:T:C	F317L	0.999
16:3119611:C:A	F317L	0.999
16:3119611:C:G	F317L	0.999
16:3119693:T:C	F345L	0.999
16:3119695:C:A	F345L	0.999
16:3119695:C:G	F345L	0.999
16:3119804:C:G	H382D	0.999

dbSNP variants (sampled 300 via entrez): RS1000057340 (16:3117352 G>A), RS1000131613 (16:3111222 G>A,C), RS1000341512 (16:3115738 G>A,T), RS1000561731 (16:3113896 AGT>A,AGTGT,AGTGTGT), RS1001020560 (16:3115616 G>T), RS1001060113 (16:3118632 C>A,T), RS1001193096 (16:3111852 G>A), RS1002049966 (16:3113598 G>A,C,T), RS1002081075 (16:3113373 GC>G), RS1002300888 (16:3118351 A>G), RS1002401744 (16:3115981 G>A,T), RS1002665369 (16:3117489 C>A,G), RS1002738968 (16:3117194 G>C), RS1002938481 (16:3112681 C>T), RS1003250107 (16:3113892 G>A)

Disease associations

OMIM: gene MIM:603436 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
butyraldehyde	decreases expression	1
jinfukang	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Caffeine	decreases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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