ZNF449

Summary

ZNF449 (zinc finger protein 449, HGNC:21039) is a protein-coding gene on chromosome Xq26.3, encoding Zinc finger protein 449 (Q6P9G9). May be involved in transcriptional regulation.

This gene encodes a nuclear protein that likely functions as a transcription factor. The protein includes an N-terminal SCAN domain, and seven C2H2-type zinc finger motifs.

Source: NCBI Gene 203523 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_152695

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21039
Approved symbol	ZNF449
Name	zinc finger protein 449
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	ZSCAN19, FLJ23614
Ensembl gene	ENSG00000173275
Ensembl biotype	protein_coding
OMIM	300627
Entrez	203523

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000339249, ENST00000370761, ENST00000850984, ENST00000887114, ENST00000912184, ENST00000912185

RefSeq mRNA: 1 — MANE Select: NM_152695 NM_152695

CCDS: CCDS14649

Canonical transcript exons

ENST00000339249 — 5 exons

Exon	Start	End
ENSE00001198094	135347019	135347472
ENSE00001433760	135360193	135363413
ENSE00001697892	135349110	135349314
ENSE00001731646	135359892	135360005
ENSE00004283145	135344796	135344835

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 95.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.6232 / max 28.7072, expressed in 1273 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197630	2.6232	1273

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.18	gold quality
epithelial cell of pancreas	CL:0000083	94.43	gold quality
secondary oocyte	CL:0000655	94.43	gold quality
adrenal tissue	UBERON:0018303	88.75	gold quality
middle temporal gyrus	UBERON:0002771	88.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.36	gold quality
left ventricle myocardium	UBERON:0006566	86.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.38	gold quality
tibialis anterior	UBERON:0001385	85.37	silver quality
deltoid	UBERON:0001476	84.89	silver quality
cartilage tissue	UBERON:0002418	84.53	gold quality
right adrenal gland cortex	UBERON:0035827	84.06	gold quality
myocardium	UBERON:0002349	83.68	gold quality
tibia	UBERON:0000979	82.86	gold quality
tendon of biceps brachii	UBERON:0008188	82.42	gold quality
right adrenal gland	UBERON:0001233	82.22	gold quality
left adrenal gland	UBERON:0001234	81.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.60	gold quality
pancreatic ductal cell	CL:0002079	81.49	silver quality
left adrenal gland cortex	UBERON:0035825	81.40	gold quality
adrenal cortex	UBERON:0001235	81.39	gold quality
visceral pleura	UBERON:0002401	81.38	gold quality
parietal pleura	UBERON:0002400	81.23	gold quality
metanephros	UBERON:0000081	81.15	gold quality
adrenal gland	UBERON:0002369	80.92	gold quality
quadriceps femoris	UBERON:0001377	80.84	silver quality
tendon	UBERON:0000043	80.40	gold quality
endothelial cell	CL:0000115	80.15	silver quality
stromal cell of endometrium	CL:0002255	79.96	gold quality
body of pancreas	UBERON:0001150	79.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1656.1	ZNF449	More than 3 adjacent zinc fingers
MA1656.2	ZNF449	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28473536

miRNA regulators (miRDB)

126 targeting ZNF449, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-497-5P	99.92	71.83	2674

Literature-anchored findings (GeneRIF, showing 2)

• ZNF449 is a member of the zinc-finger family and it may function as a transcription factor (PMID:16636917)
• During chondrogenic differentiation of human mesenchymal stem cells, ZNF449 was increased at an early stage, and its overexpression enhanced SOX9 and SOX6 only at the initial stage of the differentiation. (PMID:25546433)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp449	ENSMUSG00000073176
rattus_norvegicus	Zfp449	ENSRNOG00000050562

Paralogs (30): ZNF263 (ENSG00000006194), ZNF213 (ENSG00000085644), ZNF500 (ENSG00000103199), ZKSCAN1 (ENSG00000106261), ZNF205 (ENSG00000122386), ZSCAN9 (ENSG00000137185), PGBD1 (ENSG00000137338), ZNF215 (ENSG00000149054), ZSCAN12 (ENSG00000158691), ZNF394 (ENSG00000160908), ZNF75A (ENSG00000162086), ZSCAN21 (ENSG00000166529), ZNF232 (ENSG00000167840), ZNF24 (ENSG00000172466), 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

Zinc finger protein 449 — Q6P9G9 (reviewed: Q6P9G9)

Alternative names: Zinc finger and SCAN domain-containing protein 19

All UniProt accessions (1): Q6P9G9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P9G9-1	1	yes
Q6P9G9-2	2
Q6P9G9-3	3

RefSeq proteins (1): NP_689908* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003309	SCAN_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR038269	SCAN_sf	Homologous_superfamily

Pfam: PF00096, PF02023

UniProt features (18 total): zinc finger region 7, splice variant 4, sequence conflict 3, chain 1, domain 1, compositionally biased region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P9G9-F1	62.65	0.01

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, MARIADASON_REGULATED_BY_HISTONE_ACETYLATION_DN, GOBP_CELL_DIVISION, JEPSEN_SMRT_TARGETS, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, chrXq26, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, RBM34_TARGET_GENES, SFMBT1_TARGET_GENES, ZNF407_TARGET_GENES, ZNF423_TARGET_GENES, MIR607

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), spermatogonial cell division (GO:0007284)

GO Molecular Function (7): 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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
spermatogenesis	1
cell division	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF449	KRABD4	Q5JUW0	623
ZNF449	ZNF608	Q9ULD9	402
ZNF449	SEC14L5	O43304	396
ZNF449	PABPC5	Q96DU9	358
ZNF449	PRRC2B	Q5JSZ5	349
ZNF449	UBE4A	Q14139	336
ZNF449	SEPTIN11	Q9NVA2	330
ZNF449	GTF2IRD2B	Q6EKJ0	322
ZNF449	GTF2IRD2	Q86UP8	321
ZNF449	ZNF395	Q9H8N7	299
ZNF449	ARGFX	A6NJG6	294
ZNF449	MMGT1	Q8N4V1	286
ZNF449	SLITRK2	Q9H156	286
ZNF449	SLC10A6	Q3KNW5	285
ZNF449	GCFC2	P16383	283

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ZNF449	SCAND1	psi-mi:“MI:0915”(physical association)	0.720
SCAND1	ZNF449	psi-mi:“MI:0915”(physical association)	0.720
PIN1	ZNF449	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN22	ZNF449	psi-mi:“MI:0915”(physical association)	0.560
ZNF449	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
ZNF449	MAGOHB	psi-mi:“MI:0915”(physical association)	0.560
ZNF354C	LRP4	psi-mi:“MI:0914”(association)	0.530
ZSCAN20	ZNF197	psi-mi:“MI:0914”(association)	0.350
SCRIB	C1orf226	psi-mi:“MI:0914”(association)	0.350
SCAND1	ZNF449	psi-mi:“MI:0915”(physical association)	0.000
PIN1	ZNF449	psi-mi:“MI:0915”(physical association)	0.000
ZSCAN22	ZNF449	psi-mi:“MI:0915”(physical association)	0.000
MAGOHB	ZNF449	psi-mi:“MI:0915”(physical association)	0.000
MORF4L1	ZNF449	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): ZNF449 (Two-hybrid), ZNF449 (Affinity Capture-MS), ZNF449 (Reconstituted Complex), ZNF449 (Affinity Capture-MS), ZNF449 (Affinity Capture-RNA), ZNF449 (Two-hybrid), ZNF449 (Two-hybrid), ZNF449 (Two-hybrid), ZSCAN22 (Two-hybrid), MORF4L1 (Two-hybrid), ZNF449 (Affinity Capture-MS), ZNF449 (Affinity Capture-MS), ZNF449 (Affinity Capture-MS)

ESM2 similar proteins: A1YEQ3, A1YEV9, A1YFW6, A1YG26, A1YG48, A1YG60, A2T6W2, A2T712, A2T736, A2T7L7, A6QNZ0, O14978, O15535, O95125, P17022, P17029, P49910, P51815, P59923, Q07231, Q15776, Q16670, Q1LZ87, Q3MJ62, Q3URR7, Q4KLI1, Q4R8H9, Q53GI3, Q5R670, Q5R741, Q5RJ54, Q63HK3, Q642B9, Q6P9G9, Q810A1, Q86W11, Q8BGS3, Q8CF60, Q8NF99, Q92670

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17040, P28698, P49910, P51815, P59923

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1045 predictions. Top by Δscore:

Variant	Effect	Δscore
X:135359885:T:TA	acceptor_gain	1.0000
X:135359886:G:A	acceptor_gain	0.9900
X:135360001:GATAG:G	donor_gain	0.9900
X:135344832:GGCG:G	donor_gain	0.9800
X:135344833:GCGG:G	donor_gain	0.9800
X:135347468:AGCAG:A	donor_loss	0.9800
X:135347471:AG:A	donor_loss	0.9800
X:135347472:GGTA:G	donor_loss	0.9800
X:135347473:GT:G	donor_loss	0.9800
X:135347474:T:A	donor_loss	0.9800
X:135349105:CCCA:C	acceptor_loss	0.9800
X:135349106:CCAGG:C	acceptor_loss	0.9800
X:135349107:CAG:C	acceptor_loss	0.9800
X:135349108:A:C	acceptor_loss	0.9800
X:135349109:G:A	acceptor_loss	0.9800
X:135349321:C:T	donor_gain	0.9800
X:135359886:GGCCA:G	acceptor_loss	0.9800
X:135359887:GCCA:G	acceptor_loss	0.9800
X:135359888:CCAG:C	acceptor_loss	0.9800
X:135359889:CAGG:C	acceptor_loss	0.9800
X:135359890:A:T	acceptor_loss	0.9800
X:135359890:AG:A	acceptor_gain	0.9800
X:135359891:GG:G	acceptor_gain	0.9800
X:135360152:T:TA	acceptor_gain	0.9800
X:135359891:GGAT:G	acceptor_gain	0.9700
X:135360002:A:G	donor_gain	0.9700
X:135360002:ATAGG:A	donor_loss	0.9700
X:135360005:GGTA:G	donor_loss	0.9700
X:135360007:T:G	donor_loss	0.9700
X:135360152:T:G	acceptor_gain	0.9700

AlphaMissense

3416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:135360681:T:C	F388L	1.000
X:135360683:C:A	F388L	1.000
X:135360683:C:G	F388L	1.000
X:135360513:T:C	F332L	0.999
X:135360515:T:A	F332L	0.999
X:135360515:T:G	F332L	0.999
X:135360597:T:C	F360L	0.999
X:135360599:C:A	F360L	0.999
X:135360599:C:G	F360L	0.999
X:135360682:T:C	F388S	0.999
X:135360700:T:C	L394P	0.999
X:135360765:T:C	F416L	0.999
X:135360767:T:A	F416L	0.999
X:135360767:T:G	F416L	0.999
X:135360849:T:C	F444L	0.999
X:135360851:T:A	F444L	0.999
X:135360851:T:G	F444L	0.999
X:135360933:T:C	F472L	0.999
X:135360935:T:A	F472L	0.999
X:135360935:T:G	F472L	0.999
X:135360952:T:C	L478P	0.999
X:135360962:T:A	H481Q	0.999
X:135360962:T:G	H481Q	0.999
X:135361017:T:C	F500L	0.999
X:135361019:C:A	F500L	0.999
X:135361019:C:G	F500L	0.999
X:135360514:T:C	F332S	0.998
X:135360532:T:C	L338P	0.998
X:135360542:T:A	H341Q	0.998
X:135360542:T:G	H341Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000067138 (X:135356472 C>T), RS1000125013 (X:135345515 G>A), RS1001105754 (X:135347916 T>C), RS1001304964 (X:135344850 G>A,T), RS1001437664 (X:135355207 G>T), RS1002436985 (X:135357815 A>G), RS1002746699 (X:135343573 C>A), RS1002910165 (X:135353104 T>A), RS1003111509 (X:135352522 A>G), RS1004087393 (X:135352235 T>A), RS1004143700 (X:135345303 G>A), RS1004467362 (X:135363843 G>A), RS1004692927 (X:135351797 T>A), RS1005046122 (X:135355051 T>C), RS1005150958 (X:135344386 C>T)

Disease associations

OMIM: gene MIM:300627 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ferrous chloride	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Acetaminophen	increases expression	1
Gemcitabine	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Clorgyline	increases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Urethane	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XW48	HEK293 eGFP-ZNF449	Transformed cell line	Female

Clinical trials (associated diseases)

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