PHF21B

Summary

PHF21B (PHD finger protein 21B, HGNC:25161) is a protein-coding gene on chromosome 22q13.31, encoding PHD finger protein 21B (Q96EK2).

Predicted to enable zinc ion binding activity.

Source: NCBI Gene 112885 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_138415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25161
Approved symbol	PHF21B
Name	PHD finger protein 21B
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	BHC80L, FLJ34161
Ensembl gene	ENSG00000056487
Ensembl biotype	protein_coding
OMIM	616727
Entrez	112885

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000313237, ENST00000403565, ENST00000414269, ENST00000420689, ENST00000460507, ENST00000462631, ENST00000474327, ENST00000490679, ENST00000491522, ENST00000495348, ENST00000629843, ENST00000924685

RefSeq mRNA: 5 — MANE Select: NM_138415 NM_001135862, NM_001242450, NM_001284296, NM_001413063, NM_138415

CCDS: CCDS14061, CCDS46727, CCDS56234, CCDS63504

Canonical transcript exons

ENST00000313237 — 13 exons

Exon	Start	End
ENSE00000657038	44913822	44914088
ENSE00001212446	45009496	45010005
ENSE00003466516	44920398	44920490
ENSE00003478029	44916280	44916630
ENSE00003564849	45008545	45008610
ENSE00004016217	44893457	44893533
ENSE00004016218	44885863	44885938
ENSE00004016219	44885426	44885529
ENSE00004016220	44889760	44889782
ENSE00004016221	44881162	44883304
ENSE00004016224	44887963	44888121
ENSE00004016225	44896032	44896083
ENSE00004016227	44891306	44891360

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 93.06.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2481 / max 71.9652, expressed in 486 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194553	1.3568	431
194550	0.4728	184
194552	0.3372	193
194551	0.0813	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	93.06	gold quality
adenohypophysis	UBERON:0002196	89.96	gold quality
pituitary gland	UBERON:0000007	89.57	gold quality
ventricular zone	UBERON:0003053	85.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.22	gold quality
cortical plate	UBERON:0005343	80.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.89	gold quality
endocervix	UBERON:0000458	79.01	gold quality
prostate gland	UBERON:0002367	73.92	gold quality
left testis	UBERON:0004533	73.75	gold quality
uterine cervix	UBERON:0000002	73.73	gold quality
right testis	UBERON:0004534	73.08	gold quality
caudate nucleus	UBERON:0001873	72.79	gold quality
amygdala	UBERON:0001876	72.70	gold quality
testis	UBERON:0000473	72.20	gold quality
ectocervix	UBERON:0012249	72.16	gold quality
nucleus accumbens	UBERON:0001882	71.92	gold quality
left ovary	UBERON:0002119	71.59	gold quality
putamen	UBERON:0001874	71.30	gold quality
right ovary	UBERON:0002118	71.09	gold quality
anterior cingulate cortex	UBERON:0009835	70.48	gold quality
right lobe of thyroid gland	UBERON:0001119	70.08	gold quality
left lobe of thyroid gland	UBERON:0001120	69.92	gold quality
right frontal lobe	UBERON:0002810	69.91	gold quality
thyroid gland	UBERON:0002046	69.43	gold quality
body of uterus	UBERON:0009853	69.11	gold quality
forebrain	UBERON:0001890	69.05	gold quality
hypothalamus	UBERON:0001898	68.53	gold quality
ovary	UBERON:0000992	68.20	gold quality
islet of Langerhans	UBERON:0000006	67.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	6.61
E-ANND-3	yes	3.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting PHF21B, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6507-5P	99.36	70.46	2524

Literature-anchored findings (GeneRIF, showing 3)

• These data suggest that PHF21B is a novel tumor suppressor gene that can be inactivated by genetic and epigenetic mechanisms in the human cancer. (PMID:25454821)
• PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. (PMID:27777418)
• PHF21B constitutively activated wnt/beta-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2, which promotes prostate cancer stem cell-like phenotype. (PMID:28645312)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf21b	ENSDARG00000109502
mus_musculus	Phf21b	ENSMUSG00000016624
rattus_norvegicus	Phf21b	ENSRNOG00000013067

Paralogs (5): ZMYND11 (ENSG00000015171), ZMYND8 (ENSG00000101040), PHF12 (ENSG00000109118), PHF21A (ENSG00000135365), AIRE (ENSG00000160224)

Protein

Protein identifiers

PHD finger protein 21B — Q96EK2 (reviewed: Q96EK2)

All UniProt accessions (6): A0A0S2Z665, A0A0S2Z6R3, B0QYW2, B1AHC5, Q96EK2, B1AHC6

Isoforms (3)

UniProt ID	Names	Canonical?
Q96EK2-1	1	yes
Q96EK2-3	2, 3
Q96EK2-4	3

RefSeq proteins (5): NP_001129334, NP_001229379, NP_001271225, NP_001399992, NP_612424* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019787	Znf_PHD-finger	Domain

Pfam: PF00628

UniProt features (13 total): region of interest 5, splice variant 2, compositionally biased region 2, chain 1, zinc finger region 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EK2-F1	60.69	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): RRAGTTGT_UNKNOWN, PAX4_01, AREB6_01, TAL1ALPHAE47_01, GGCNKCCATNK_UNKNOWN, GATA3_01, FREAC3_01, ATTCTTT_MIR186, AACTTT_UNKNOWN, WHN_B, TAATGTG_MIR323, GGCNNMSMYNTTG_UNKNOWN, TAL1BETAE47_01, SENESE_HDAC3_TARGETS_DN, YGCGYRCGC_UNKNOWN

GO Biological Process (0):

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

1241 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF21B	HMG20A	Q9NP66	700
PHF21B	RCOR3	Q9P2K3	639
PHF21B	HSPA1A	P08107	608
PHF21B	CTBP1	Q13363	542
PHF21B	RREB1	Q92766	479
PHF21B	A6NDT3	A6NDT3	477
PHF21B	PHF24	Q9UPV7	379
PHF21B	ARSA	P15289	364
PHF21B	RCOR2	Q8IZ40	364
PHF21B	HMG20B	Q9P0W2	356
PHF21B	PHF3	Q92576	348
PHF21B	EDRF1	Q3B7T1	348
PHF21B	TBC1D22A	Q8WUA7	336
PHF21B	ZFYVE28	Q9HCC9	333
PHF21B	GSE1	Q14687	317

IntAct

6 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
PHF21B	KDM1A	psi-mi:“MI:0914”(association)	0.350
RCOR1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
SCARA3	COCH	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): PHF21B (Affinity Capture-MS), BANP (Two-hybrid), RCOR3 (Two-hybrid), TFCP2 (Two-hybrid), PHF21B (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR3 (Affinity Capture-MS), PHF13 (Affinity Capture-MS), LTF (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), MPO (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A8 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), PHF21B (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IYX6, A1L1F6, A2VCZ5, A3KP40, A5X7A0, A7MB40, A7XYJ6, B7ZS37, E1BE02, E7F888, E9Q2Z1, O35261, O35914, O95402, P59598, P78312, P98177, Q04891, Q4G112, Q53TQ3, Q566I1, Q5W1J6, Q5ZJ69, Q60795, Q66JY2, Q71F56, Q76I79, Q7YR76, Q8AYC2, Q8BHZ4, Q8BZ32, Q8CCJ9, Q8CGI1, Q8IZQ8, Q8K4J6, Q8N365, Q8R4I1, Q8R5I7, Q8VIM5, Q90WM5

Diamond homologs: A1YVX4, A2AUY4, A2BIL7, A6H619, A7E320, A8DZJ1, A9LMC0, B6CHA3, B7ZS37, B9RU15, E7EZF3, F4I240, F4KBP5, F6UA42, G5EBZ4, O43918, O88379, P29375, P41229, P41230, P47156, P56163, P58267, P58268, P58269, P58270, Q09477, Q12830, Q22516, Q23590, Q2T9V9, Q30DN6, Q38JA7, Q3UXZ9, Q4V7A6, Q5F3R2, Q5F489, Q5SMU7, Q5TKR9, Q5XUN4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3674 predictions. Top by Δscore:

Variant	Effect	Δscore
22:44883300:CATTT:C	acceptor_gain	1.0000
22:44883301:ATTT:A	acceptor_gain	1.0000
22:44883302:TTT:T	acceptor_gain	1.0000
22:44883304:TC:T	acceptor_loss	1.0000
22:44883306:T:G	acceptor_loss	1.0000
22:44885527:TGA:T	acceptor_gain	1.0000
22:44885530:C:CC	acceptor_gain	1.0000
22:44885862:CCTGT:C	donor_gain	1.0000
22:44887955:T:TA	donor_gain	1.0000
22:44887959:GTAC:G	donor_loss	1.0000
22:44887960:TAC:T	donor_loss	1.0000
22:44887961:AC:A	donor_loss	1.0000
22:44887962:C:CG	donor_loss	1.0000
22:44887962:CCTT:C	donor_gain	1.0000
22:44887994:C:CA	donor_gain	1.0000
22:44888117:TCGTT:T	acceptor_gain	1.0000
22:44888118:CGTT:C	acceptor_gain	1.0000
22:44888118:CGTTC:C	acceptor_gain	1.0000
22:44888120:TT:T	acceptor_gain	1.0000
22:44888120:TTC:T	acceptor_loss	1.0000
22:44888121:TCTG:T	acceptor_loss	1.0000
22:44888122:C:CC	acceptor_gain	1.0000
22:44888122:CTGGA:C	acceptor_loss	1.0000
22:44888123:T:A	acceptor_loss	1.0000
22:44891300:GCTTA:G	donor_loss	1.0000
22:44891301:CTTA:C	donor_loss	1.0000
22:44891302:TTA:T	donor_loss	1.0000
22:44891304:A:AT	donor_loss	1.0000
22:44891305:C:A	donor_loss	1.0000
22:44891305:CCT:C	donor_gain	1.0000

AlphaMissense

3416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:44893499:T:A	R306S	0.999
22:44893499:T:G	R306S	0.999
22:44893500:C:G	R306T	0.999
22:44893502:T:A	R305S	0.999
22:44893502:T:G	R305S	0.999
22:44893505:C:A	K304N	0.999
22:44893505:C:G	K304N	0.999
22:44893509:C:G	R303P	0.999
22:44896055:A:G	L287P	0.999
22:44893491:G:T	A309D	0.998
22:44893496:G:C	S307R	0.998
22:44893496:G:T	S307R	0.998
22:44893498:T:G	S307R	0.998
22:44893503:C:G	R305T	0.998
22:44896072:G:C	F281L	0.998
22:44896072:G:T	F281L	0.998
22:44896074:A:G	F281L	0.998
22:44893492:C:G	A309P	0.997
22:44893518:C:G	R300P	0.997
22:44896052:A:T	V288D	0.997
22:44896058:C:A	G286V	0.997
22:44896061:A:G	L285P	0.997
22:44896065:C:G	A284P	0.997
22:44896073:A:G	F281S	0.997
22:44885505:A:G	L433P	0.996
22:44887983:A:G	C393R	0.996
22:44893501:T:C	R306G	0.996
22:44893507:T:C	K304E	0.996
22:44896069:C:A	M282I	0.996
22:44896069:C:G	M282I	0.996

dbSNP variants (sampled 300 via entrez): RS1000007983 (22:44930954 G>A,C), RS1000041694 (22:44969913 T>A), RS1000079843 (22:44939681 C>A), RS1000087375 (22:44911420 G>A), RS1000100677 (22:44941662 C>G,T), RS1000108302 (22:45011786 C>G), RS1000119172 (22:44939101 T>A,C), RS1000139255 (22:44996405 AAAC>A), RS1000178222 (22:44904879 T>G), RS1000186393 (22:44904895 C>A), RS1000202123 (22:44965329 G>A), RS1000211884 (22:44933431 T>A,C,G), RS1000260622 (22:44960775 T>C,G), RS1000322670 (22:44900481 A>C), RS1000329275 (22:45000501 T>A)

Disease associations

OMIM: gene MIM:616727 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002593_28	Dementia and core Alzheimer’s disease neuropathologic changes	2.000000e-08
GCST002593_51	Dementia and core Alzheimer’s disease neuropathologic changes	2.000000e-08
GCST002938_31	Copper levels	6.000000e-06
GCST003074_25	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	2.000000e-07
GCST005231_24	Major depressive disorder	2.000000e-06
GCST006138_16	Resting-state electroencephalogram vigilance	9.000000e-06
GCST007465_17	Phoneme awareness	8.000000e-06
GCST012616_7	Spondylosis	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004357	electroencephalogram measurement
EFO:0005301	reading and spelling ability

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	affects cotreatment, increases expression	3
Valproic Acid	affects expression, increases methylation	2
bisphenol A	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	affects methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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