PASD1

Summary

PASD1 (PAS domain containing repressor 1, HGNC:20686) is a protein-coding gene on chromosome Xq28, encoding Circadian clock protein PASD1 (Q8IV76). Functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body.

This gene encodes a protein that is thought to function as a transcription factor. The protein is a cancer-associated antigen that can stimulate autologous T-cell responses, and it is therefore considered to be a potential immunotherapeutic target for the treatment of various hematopoietic malignancies, including diffuse large B-cell lymphoma.

Source: NCBI Gene 139135 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 144 total
• MANE Select transcript: NM_173493

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20686
Approved symbol	PASD1
Name	PAS domain containing repressor 1
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	CT63
Ensembl gene	ENSG00000166049
Ensembl biotype	protein_coding
OMIM	300993
Entrez	139135

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000370357, ENST00000464219

RefSeq mRNA: 1 — MANE Select: NM_173493 NM_173493

CCDS: CCDS35431

Canonical transcript exons

ENST00000370357 — 16 exons

Exon	Start	End
ENSE00001241600	151673928	151674186
ENSE00001241606	151672183	151672661
ENSE00001241683	151563675	151563839
ENSE00001452459	151675997	151676739
ENSE00003469859	151620930	151621029
ENSE00003475474	151622937	151623064
ENSE00003476128	151625448	151625530
ENSE00003479675	151664119	151664348
ENSE00003525557	151601527	151601581
ENSE00003539799	151648615	151648702
ENSE00003549695	151611664	151611753
ENSE00003553903	151621482	151621592
ENSE00003601468	151604646	151604734
ENSE00003602117	151659713	151659836
ENSE00003610357	151671573	151671779
ENSE00003630099	151671038	151671196

Expression profiles

Bgee: expression breadth broad, 12 present calls, max score 83.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4234 / max 70.1910, expressed in 55 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197992	0.3336	52
197993	0.0898	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.17	gold quality
right testis	UBERON:0004534	80.31	gold quality
left testis	UBERON:0004533	78.94	gold quality
testis	UBERON:0000473	78.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.44	gold quality
pancreatic ductal cell	CL:0002079	71.90	silver quality
tibialis anterior	UBERON:0001385	59.37	silver quality
secondary oocyte	CL:0000655	58.98	gold quality
epithelial cell of pancreas	CL:0000083	56.09	gold quality
skin of hip	UBERON:0001554	54.76	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
sperm	CL:0000019	53.59	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	52.86	gold quality
adult organism	UBERON:0007023	52.55	gold quality
oocyte	CL:0000023	52.39	gold quality
ileal mucosa	UBERON:0000331	51.54	silver quality
upper leg skin	UBERON:0004262	51.12	silver quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	49.02	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
vastus lateralis	UBERON:0001379	46.95	gold quality
pylorus	UBERON:0001166	46.84	gold quality
tendon of biceps brachii	UBERON:0008188	46.07	gold quality
layer of synovial tissue	UBERON:0007616	45.85	gold quality
buccal mucosa cell	CL:0002336	45.64	gold quality
biceps brachii	UBERON:0001507	45.50	gold quality
amniotic fluid	UBERON:0000173	45.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.09

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CLOCK	Repression

miRNA regulators (miRDB)

31 targeting PASD1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-4771	97.43	67.69	596
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4791	96.51	67.76	659

Literature-anchored findings (GeneRIF, showing 5)

• PASD1-derived epitopes are both efficiently and selectively processed and presented by native human multiple myeloma cells as cancer vaccines. (PMID:20861911)
• PASD1 is a circadian bHLH-PAS paralog repressor of CLOCK protein expression. (PMID:25936801)
• PASD1 serves as a critical nuclear positive regulator of STAT3-mediated gene expression and tumorigenesis. (PMID:26892021)
• Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. (PMID:31478431)
• Findings suggested that PASD1 expression in glioma patients was extremely upregulated compared with that in normal tissue samples and cell lines. (PMID:31558691)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	npas2	ENSDARG00000016536
mus_musculus	Pasd1	ENSMUSG00000073130
rattus_norvegicus	Pasd1	ENSRNOG00000061428
drosophila_melanogaster	Met	FBGN0002723
drosophila_melanogaster	Clk	FBGN0023076
drosophila_melanogaster	gce	FBGN0261703
drosophila_melanogaster	tgo	FBGN0264075
caenorhabditis_elegans	aha-1	WBGENE00000095

Paralogs (6): BMAL2 (ENSG00000029153), BMAL1 (ENSG00000133794), CLOCK (ENSG00000134852), ARNT (ENSG00000143437), NPAS2 (ENSG00000170485), ARNT2 (ENSG00000172379)

Protein

Protein identifiers

Circadian clock protein PASD1 — Q8IV76 (reviewed: Q8IV76)

Alternative names: Cancer/testis antigen 63, OX-TES-1, PAS domain-containing protein 1

All UniProt accessions (1): Q8IV76

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body. Acts as a nuclear repressor of the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock components. Inhibits circadian clock function in cancer cells, when overexpressed.

Subunit / interactions. Interacts with the CLOCK-BMAL1 heterodimer; this interaction inhibits CLOCK-BMAL1 transcriptional activation and suppress circadian timekeeping. Interacts with BMAL1.

Subcellular location. Nucleus Nucleus.

Tissue specificity. Testis-specific. Expressed in a broad range of cancer cells, including melanoma, lung cancer, and breast cancer (at protein level). Testis-specific. Found in histologically normal tissues from patients with uterus, lung and small intestine cancers. Widespread expression seen in solid tumors and diffuse large B-cell lymphoma (DLBCL)-derived cell lines. Isoform 2 is expressed in all DLBCL-derived cell lines, while isoform 1 is preferentially expressed in cell lines derived from non-germinal center DLBCL.

Domain organisation. C-termini of isoform 1 and isoform 2 are sufficient to interact with and to repress the activity of CLOCK-BMAL1.

Miscellaneous. Due to intron retention.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IV76-1	1, PASD1_v2	yes
Q8IV76-2	2, PASD1_v1

RefSeq proteins (1): NP_775764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR047230	CLOCK-like	Family

UniProt features (16 total): region of interest 5, splice variant 2, mutagenesis site 2, coiled-coil region 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV76-F1	53.39	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
36	reduces inhibition of clock-bmal1 heterodimer activity; when associated with r-45.
45	reduces inhibition of clock-bmal1 heterodimer activity; when associated with e-36.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_CIRCADIAN_RHYTHM, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_TRANSCRIPTION_REPRESSOR_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOBP_RHYTHMIC_PROCESS, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrXq28

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), circadian regulation of gene expression (GO:0032922), negative regulation of circadian rhythm (GO:0042754), negative regulation of DNA-templated transcription (GO:0045892), regulation of gene expression (GO:0010468), rhythmic process (GO:0048511)

GO Molecular Function (3): DNA-binding transcription factor binding (GO:0140297), transcription regulator inhibitor activity (GO:0140416), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)

GO Cellular Component (4): nucleus (GO:0005634), nuclear speck (GO:0016607), Cry-Per complex (GO:1990512), CLOCK-BMAL transcription complex (GO:1990513)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
circadian rhythm	2
regulation of gene expression	2
transcription by RNA polymerase II	1
regulation of circadian rhythm	1
negative regulation of biological process	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
biological_process	1
transcription factor binding	1
transcription regulator activity	1
molecular function inhibitor activity	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
intracellular membrane-bounded organelle	1
nuclear ribonucleoprotein granule	1
transcription repressor complex	1
nuclear protein-containing complex	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PASD1	BMAL1	O00327	660
PASD1	CTAG2	O75638	517
PASD1	DDX43	Q9NXZ2	511
PASD1	CT45A1	Q5HYN5	506
PASD1	ACTL8	Q9H568	505
PASD1	MAGEA3	P43357	496
PASD1	CT55	Q8WUE5	493
PASD1	CTAG1A	P78358	479
PASD1	GAGE2A	Q6NT46	479
PASD1	A0A1W2PQG5	A0A1W2PQG5	479
PASD1	CSAG2	Q9Y5P2	473
PASD1	NXF2B	Q9GZY0	462
PASD1	MS4A12	Q9NXJ0	457
PASD1	SSX1	Q16384	456
PASD1	SCGB1D2	O95969	449

IntAct

6 interactions, top by confidence:

A	B	Type	Score
BMAL1	CLOCK	psi-mi:“MI:0914”(association)	0.880
BMAL1	PASD1	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (3): PASD1 (Affinity Capture-RNA), PASD1 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GVQ3, A0A1W2PPK0, A0A1W2PPM1, A2A9I7, A6NCI8, A6QQS3, A7XCE8, E9PI22, E9PXT9, O15016, O91083, P09414, P0DMB1, P17923, P18804, P20879, P35965, P49750, Q0P670, Q12857, Q1RMX6, Q32LN6, Q32MG2, Q3B8N5, Q3T016, Q3V0A6, Q4JK59, Q5BI31, Q5T035, Q5ZKH6, Q642A3, Q6AXV6, Q6IMN6, Q6P1W5, Q6PEX7, Q6X4T0, Q80YD3, Q86UF4, Q8BII1, Q8C5V0

Diamond homologs: A0MLS5, O00327, O08785, O09000, O15516, O61735, O88529, P70365, P97460, Q15788, Q4PJW2, Q5R4T2, Q5RAK8, Q5ZQU2, Q6YGZ4, Q6YGZ5, Q8IV76, Q8QGQ6, Q8QGQ7, Q91YA8, Q91YA9, Q91YB0, Q91YB2, Q99743, Q9EPW1, Q9I8T7, Q9WTL8, Q9WVS9, Q9Y6Q9, A9YTQ3, O61734, O70361, P56645, Q3U1U7, Q75NT5, Q8CJE2, P12348

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	21
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2700 predictions. Top by Δscore:

Variant	Effect	Δscore
X:151601526:GGA:G	acceptor_gain	1.0000
X:151604640:A:AG	acceptor_gain	1.0000
X:151604641:A:G	acceptor_gain	1.0000
X:151611306:A:T	donor_gain	1.0000
X:151611754:G:GG	donor_gain	1.0000
X:151619889:G:GT	donor_gain	1.0000
X:151619890:A:T	donor_gain	1.0000
X:151648614:GTA:G	acceptor_gain	1.0000
X:151648700:GAC:G	donor_gain	1.0000
X:151648703:G:GG	donor_gain	1.0000
X:151659700:T:TA	acceptor_gain	1.0000
X:151659701:G:A	acceptor_gain	1.0000
X:151664117:A:AG	acceptor_gain	1.0000
X:151664118:G:GG	acceptor_gain	1.0000
X:151664118:GCCTT:G	acceptor_gain	1.0000
X:151672175:C:A	acceptor_gain	1.0000
X:151563837:AGGGT:A	donor_loss	0.9900
X:151563838:GG:G	donor_gain	0.9900
X:151563839:GG:G	donor_gain	0.9900
X:151563839:GGTG:G	donor_loss	0.9900
X:151563840:G:GA	donor_loss	0.9900
X:151563841:T:A	donor_loss	0.9900
X:151601521:TTTCA:T	acceptor_loss	0.9900
X:151601522:TTCA:T	acceptor_loss	0.9900
X:151601523:TCAG:T	acceptor_loss	0.9900
X:151601525:A:C	acceptor_loss	0.9900
X:151601526:G:GC	acceptor_loss	0.9900
X:151601578:AGAGG:A	donor_loss	0.9900
X:151601579:GAGG:G	donor_loss	0.9900
X:151601580:AGGTA:A	donor_loss	0.9900

AlphaMissense

5110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:151621496:T:C	F108L	0.992
X:151621498:T:A	F108L	0.992
X:151621498:T:G	F108L	0.992
X:151621497:T:C	F108S	0.988
X:151611676:T:C	F44L	0.983
X:151611678:T:A	F44L	0.983
X:151611678:T:G	F44L	0.983
X:151620952:T:C	L77S	0.972
X:151621563:T:C	F130S	0.972
X:151620964:T:C	L81P	0.967
X:151621497:T:G	F108C	0.967
X:151621502:T:C	C110R	0.966
X:151621509:T:C	L112S	0.965
X:151621504:T:G	C110W	0.958
X:151611701:G:T	G52V	0.953
X:151611677:T:C	F44S	0.951
X:151620964:T:A	L81Q	0.947
X:151620964:T:G	L81R	0.946
X:151611683:T:G	I46S	0.942
X:151623029:G:A	G171R	0.942
X:151623029:G:C	G171R	0.942
X:151623030:G:A	G171E	0.942
X:151621562:T:C	F130L	0.941
X:151621564:T:A	F130L	0.941
X:151621564:T:G	F130L	0.941
X:151611689:T:C	L48P	0.940
X:151611691:A:C	S49R	0.934
X:151611693:C:A	S49R	0.934
X:151611693:C:G	S49R	0.934
X:151623036:T:A	V173D	0.931

dbSNP variants (sampled 300 via entrez): RS1000016170 (X:151576450 G>A), RS1000025950 (X:151653040 G>A), RS1000069132 (X:151627327 G>A), RS1000078140 (X:151645821 C>G), RS1000099835 (X:151627849 C>A), RS1000104605 (X:151675725 G>A), RS1000160350 (X:151670843 C>A,T), RS1000237732 (X:151640424 T>C), RS1000239242 (X:151580981 T>C), RS1000258182 (X:151598424 A>G), RS1000337419 (X:151590322 C>G,T), RS1000396701 (X:151580096 C>G), RS1000457118 (X:151589720 C>A), RS1000489490 (X:151616616 T>G), RS1000562212 (X:151675233 G>A)

Disease associations

OMIM: gene MIM:300993 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1

Clinical trials (associated diseases)

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