PIH1D2

Summary

PIH1D2 (PIH1 domain containing 2, HGNC:25210) is a protein-coding gene on chromosome 11q23.1, encoding PIH1 domain-containing protein 2 (Q8WWB5).

Enables small GTPase binding activity. Predicted to be involved in box C/D snoRNP assembly and rRNA processing. Part of protein folding chaperone complex.

Source: NCBI Gene 120379 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_138789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25210
Approved symbol	PIH1D2
Name	PIH1 domain containing 2
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	DNAAF15
Ensembl gene	ENSG00000150773
Ensembl biotype	protein_coding
Entrez	120379

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 non_stop_decay, 1 nonsense_mediated_decay

ENST00000280350, ENST00000431456, ENST00000521853, ENST00000525072, ENST00000525744, ENST00000528775, ENST00000530641, ENST00000532211, ENST00000676994, ENST00000957365, ENST00000957366, ENST00000957367, ENST00000957368

RefSeq mRNA: 2 — MANE Select: NM_138789 NM_001082619, NM_138789

CCDS: CCDS44730, CCDS8355

Canonical transcript exons

ENST00000280350 — 6 exons

Exon	Start	End
ENSE00000996266	112071038	112071283
ENSE00000996267	112070436	112070701
ENSE00001130661	112072998	112073205
ENSE00001557660	112073980	112074017
ENSE00002140408	112067798	112068005
ENSE00003558721	112071635	112071758

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 94.40.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5980 / max 99.7491, expressed in 735 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122304	1.5526	716
122305	0.0454	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.40	gold quality
right testis	UBERON:0004534	94.10	gold quality
right uterine tube	UBERON:0001302	92.86	gold quality
testis	UBERON:0000473	92.10	gold quality
bronchial epithelial cell	CL:0002328	91.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.51	gold quality
bronchus	UBERON:0002185	89.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.35	gold quality
sperm	CL:0000019	85.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.47	gold quality
adult organism	UBERON:0007023	84.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.09	gold quality
fallopian tube	UBERON:0003889	76.11	gold quality
oviduct epithelium	UBERON:0004804	75.71	gold quality
adenohypophysis	UBERON:0002196	75.62	gold quality
left lobe of thyroid gland	UBERON:0001120	74.58	gold quality
right lobe of thyroid gland	UBERON:0001119	74.06	gold quality
thyroid gland	UBERON:0002046	73.85	gold quality
pituitary gland	UBERON:0000007	73.41	gold quality
islet of Langerhans	UBERON:0000006	72.62	gold quality
metanephros cortex	UBERON:0010533	72.51	gold quality
hypothalamus	UBERON:0001898	71.04	gold quality
ventricular zone	UBERON:0003053	70.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.42	gold quality
right lung	UBERON:0002167	70.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.57	gold quality
caudate nucleus	UBERON:0001873	69.37	gold quality
calcaneal tendon	UBERON:0003701	69.13	gold quality
anterior cingulate cortex	UBERON:0009835	69.04	gold quality
right adrenal gland cortex	UBERON:0035827	68.88	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.85
E-MTAB-9388	yes	7.01
E-GEOD-36552	no	50.25

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pih1d2	ENSDARG00000014849
mus_musculus	Pih1d2	ENSMUSG00000000167
rattus_norvegicus	Pih1d2	ENSRNOG00000009965
drosophila_melanogaster	CG4022	FBGN0035986

Paralogs (2): PIH1D1 (ENSG00000104872), DNAAF2 (ENSG00000165506)

Protein

Protein identifiers

PIH1 domain-containing protein 2 — Q8WWB5 (reviewed: Q8WWB5)

All UniProt accessions (3): Q8WWB5, A0A0A0MTE1, H0YCC0

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. May be due to a competing donor splice site.

Similarity. Belongs to the PIH1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WWB5-1	1	yes
Q8WWB5-2	2
Q8WWB5-3	3

RefSeq proteins (2): NP_001076088, NP_620144* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012981	PIH1_N	Domain
IPR041442	PIH1D1/2/3_CS-like	Domain
IPR050734	PIH1/Kintoun_subfamily	Family

Pfam: PF08190, PF18201

UniProt features (6 total): splice variant 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWB5-F1	78.27	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_GTPASE_BINDING, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_PROTEIN_STABILIZATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, RYTTCCTG_ETS2_B, RFX1_02, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, CETS1P54_01, GOCC_RIBONUCLEOPROTEIN_COMPLEX, SCGGAAGY_ELK1_02, DODD_NASOPHARYNGEAL_CARCINOMA_DN, ELK1_02, CHYLA_CBFA2T3_TARGETS_DN

GO Biological Process (3): box C/D snoRNP assembly (GO:0000492), rRNA processing (GO:0006364), protein stabilization (GO:0050821)

GO Molecular Function (2): small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), R2TP complex (GO:0097255), protein folding chaperone complex (GO:0101031), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-containing complex	2
small nucleolar ribonucleoprotein complex assembly	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
regulation of protein stability	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIH1D2	SPAG1	Q07617	831
PIH1D2	DNAAF6	Q9NQM4	830
PIH1D2	RUVBL1	P82276	786
PIH1D2	RUVBL2	Q9Y230	782
PIH1D2	RPAP3	Q9H6T3	761
PIH1D2	DNAI1	Q9UI46	633
PIH1D2	DNAAF10	Q96MX6	623
PIH1D2	CFAP300	Q9BRQ4	591
PIH1D2	DNAAF2	Q9NVR5	591
PIH1D2	LRRC56	Q8IYG6	590
PIH1D2	DNAAF4	Q8WXU2	587
PIH1D2	NKAPD1	Q6ZUT1	572
PIH1D2	HSP90AB1	P08238	567
PIH1D2	HSP90AA1	P07900	565
PIH1D2	DNALI1	O14645	564

IntAct

253 interactions, top by confidence:

A	B	Type	Score
PIH1D2	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.720
PIH1D2	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.720
MDFI	PIH1D2	psi-mi:“MI:0915”(physical association)	0.720
PIH1D2	DPH3	psi-mi:“MI:0915”(physical association)	0.720
MRFAP1L1	PIH1D2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-4	PIH1D2	psi-mi:“MI:0915”(physical association)	0.720
PIH1D2	MDFI	psi-mi:“MI:0915”(physical association)	0.720
SPRED1	PIH1D2	psi-mi:“MI:0915”(physical association)	0.720
GFAP	PIH1D2	psi-mi:“MI:0915”(physical association)	0.670
PIH1D2	REL	psi-mi:“MI:0915”(physical association)	0.670
PIH1D2	GFAP	psi-mi:“MI:0915”(physical association)	0.670
REL	PIH1D2	psi-mi:“MI:0915”(physical association)	0.670
ITGB3BP	PIH1D2	psi-mi:“MI:0915”(physical association)	0.670
EIF4A2	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
PIH1D2		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), DPH3 (Two-hybrid), KRTAP12-4 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid), PIH1D2 (Two-hybrid)

ESM2 similar proteins: A0JMU5, A1A5P5, A3KN24, A6QLC7, A9ULH0, B2RXC1, B5DF07, B6DMK2, B6NXD5, O60678, O70467, O75417, P0C7N0, Q08B12, Q14AI0, Q19QT9, Q28ES8, Q2KI89, Q32LH3, Q32NV1, Q32PH0, Q3EBC8, Q4R6P2, Q5E9U4, Q5R629, Q5RDC7, Q5XGG3, Q5ZI89, Q5ZJM3, Q641F8, Q68F70, Q6DHJ1, Q6GMB0, Q6GPP1, Q6NU25, Q6PBV4, Q6PD74, Q7Z392, Q8BP74, Q8BSA9

Diamond homologs: B5BUZ8, B6F1W5, Q32LH3, Q5XGG3, Q7ZWY2, Q8WWB5, Q5PRB3, Q8CHR9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PIH1D2	“form complex”	“R2SP co-chaperone”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1033 predictions. Top by Δscore:

Variant	Effect	Δscore
11:112070517:A:AC	donor_gain	0.9900
11:112070518:C:CC	donor_gain	0.9900
11:112071296:T:TC	acceptor_gain	0.9900
11:112070491:TTCA:T	donor_gain	0.9800
11:112070499:A:AC	donor_gain	0.9800
11:112070706:A:C	acceptor_gain	0.9800
11:112071290:G:C	acceptor_gain	0.9800
11:112071290:G:GC	acceptor_gain	0.9800
11:112073759:TTCTC:T	donor_gain	0.9800
11:112073760:T:TA	donor_gain	0.9800
11:112073760:TCTCT:T	donor_gain	0.9800
11:112070704:T:C	acceptor_gain	0.9700
11:112070706:A:AC	acceptor_gain	0.9700
11:112072993:CAT:C	donor_loss	0.9700
11:112072994:AT:A	donor_loss	0.9700
11:112072995:TAC:T	donor_loss	0.9700
11:112072996:A:AT	donor_loss	0.9700
11:112072997:C:CA	donor_loss	0.9700
11:112070513:T:TA	donor_gain	0.9600
11:112070702:C:CC	acceptor_gain	0.9600
11:112071114:T:TA	donor_gain	0.9600
11:112071203:A:C	donor_gain	0.9600
11:112072991:GACAT:G	donor_loss	0.9600
11:112072992:ACATA:A	donor_loss	0.9600
11:112073893:A:C	donor_gain	0.9600
11:112070704:T:TC	acceptor_gain	0.9500
11:112072996:A:AC	donor_gain	0.9500
11:112072997:C:CC	donor_gain	0.9500
11:112071759:C:CC	acceptor_gain	0.9400
11:112071036:ACC:A	donor_gain	0.9300

AlphaMissense

2088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:112071719:A:G	W73R	0.973
11:112071719:A:T	W73R	0.973
11:112067916:A:C	F301L	0.964
11:112067916:A:T	F301L	0.964
11:112067918:A:G	F301L	0.964
11:112073129:A:G	W16R	0.964
11:112073129:A:T	W16R	0.964
11:112067924:C:G	A299P	0.958
11:112067896:A:G	L308P	0.953
11:112071259:G:T	A109D	0.952
11:112067917:A:G	F301S	0.945
11:112073127:C:A	W16C	0.939
11:112073127:C:G	W16C	0.939
11:112070449:A:G	L267P	0.934
11:112067923:G:T	A299E	0.932
11:112073122:A:G	L18P	0.927
11:112070488:A:T	V254D	0.926
11:112071729:G:C	N69K	0.923
11:112071729:G:T	N69K	0.923
11:112070482:A:G	L256S	0.919
11:112071735:A:C	F67L	0.917
11:112071735:A:T	F67L	0.917
11:112071737:A:G	F67L	0.917
11:112073077:A:G	F33S	0.917
11:112073110:A:G	L22P	0.913
11:112071717:C:A	W73C	0.912
11:112071717:C:G	W73C	0.912
11:112067968:A:G	L284S	0.911
11:112071262:A:T	V108D	0.910
11:112071260:C:G	A109P	0.907

dbSNP variants (sampled 300 via entrez): RS1000299707 (11:112062615 G>A,T), RS1000411451 (11:112070192 T>C), RS1000856537 (11:112075312 C>T), RS1000864139 (11:112069820 C>A,T), RS1001475776 (11:112061686 C>A), RS1001581733 (11:112069708 G>A), RS1001985972 (11:112055109 T>C), RS1002032317 (11:112069223 G>A), RS1002775474 (11:112074499 C>A,G), RS1003044865 (11:112060699 C>T), RS1003096990 (11:112060230 C>G,T), RS1003399600 (11:112053486 T>A,C), RS1003632171 (11:112066041 A>G), RS1003753428 (11:112073320 G>C,T), RS1003784273 (11:112072910 T>A,G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:245348

GenCC curated gene-disease

Mondo (1): pyruvate dehydrogenase E2 deficiency (MONDO:0009502)

Orphanet (2): Pyruvate dehydrogenase deficiency (Orphanet:765), Pyruvate dehydrogenase E2 deficiency (Orphanet:79244)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_266	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565448	Pyruvate Dehydrogenase E2 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression	1
beta-lapachone	increases expression, decreases expression	1
bisphenol S	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05257005	Not specified	UNKNOWN	Natural History Study of Pyruvate Dehydrogenase Deficiency