CIROZ

Summary

CIROZ (ciliated left-right organizer protein containing ZP-N domains, HGNC:26730) is a protein-coding gene on chromosome 1p36.22, encoding Ciliated left-right organizer ZP-N domains-containing protein (Q8N9H9). Plays a role in left-right patterning process.

Predicted to act upstream of or within determination of left/right symmetry and heart development.

Source: NCBI Gene 148345 — RefSeq curated summary.

At a glance

• Gene–disease (curated): visceral heterotaxy (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 19 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 59
• MANE Select transcript: NM_001170754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26730
Approved symbol	CIROZ
Name	ciliated left-right organizer protein containing ZP-N domains
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37118
Ensembl gene	ENSG00000175262
Ensembl biotype	protein_coding
OMIM	619700
Entrez	148345

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000377004, ENST00000418570, ENST00000468348, ENST00000476357, ENST00000520253

RefSeq mRNA: 2 — MANE Select: NM_001170754 NM_001170754, NM_001366227

CCDS: CCDS53267

Canonical transcript exons

ENST00000377004 — 13 exons

Exon	Start	End
ENSE00001262890	10949624	10949814
ENSE00001262930	10947643	10948844
ENSE00003272129	10954990	10955186
ENSE00003317474	10958714	10958752
ENSE00003331205	10957616	10957753
ENSE00003331392	10954019	10954142
ENSE00003389747	10957023	10957107
ENSE00003573257	10982012	10982076
ENSE00003611980	10964128	10964271
ENSE00003660665	10969970	10970089
ENSE00003665854	10966358	10966482
ENSE00003685308	10976156	10976256
ENSE00003975998	10946475	10946741

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 87.88.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.88	gold quality
islet of Langerhans	UBERON:0000006	84.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.57	gold quality
muscle of leg	UBERON:0001383	76.67	gold quality
gastrocnemius	UBERON:0001388	76.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.87	gold quality
skeletal muscle tissue	UBERON:0001134	75.22	gold quality
nasal cavity epithelium	UBERON:0005384	74.10	gold quality
pancreas	UBERON:0001264	72.86	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.13	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.92	gold quality
muscle tissue	UBERON:0002385	71.77	gold quality
myocardium	UBERON:0002349	71.30	gold quality
sperm	CL:0000019	69.86	gold quality
body of pancreas	UBERON:0001150	68.68	gold quality
buccal mucosa cell	CL:0002336	67.23	silver quality
epithelium of nasopharynx	UBERON:0001951	65.80	gold quality
heart right ventricle	UBERON:0002080	64.32	gold quality
apex of heart	UBERON:0002098	64.17	gold quality
monocyte	CL:0000576	64.16	gold quality
leukocyte	CL:0000738	64.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	63.54	gold quality
lateral nuclear group of thalamus	UBERON:0002736	63.43	gold quality
secondary oocyte	CL:0000655	63.40	gold quality
granulocyte	CL:0000094	63.15	gold quality
endothelial cell	CL:0000115	63.00	gold quality
tendon of biceps brachii	UBERON:0008188	62.51	gold quality
substantia nigra pars compacta	UBERON:0001965	62.21	gold quality
cerebellar cortex	UBERON:0002129	61.51	gold quality
cerebellar hemisphere	UBERON:0002245	61.43	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	20.54
E-MTAB-5061	yes	19.99
E-GEOD-81547	yes	13.61
E-GEOD-83139	yes	9.81
E-ANND-3	yes	3.09
E-ENAD-27	no	71.05

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-129o18.4	ENSDARG00000098029
mus_musculus	Gm572	ENSMUSG00000070577
rattus_norvegicus	C5h1orf127	ENSRNOG00000023452

Protein

Protein identifiers

Ciliated left-right organizer ZP-N domains-containing protein — Q8N9H9 (reviewed: Q8N9H9)

Alternative names: Ciliated left-right organizer protein containing ZP-N domains

All UniProt accessions (5): G8JLG8, H0YBK5, Q8N9H9, H3BM07, K7EPZ7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in left-right patterning process.

Subcellular location. Secreted.

Disease relevance. Heterotaxy, visceral, 14, autosomal (HTX14) [MIM:621080] A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX14 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N9H9-1	1	yes
Q8N9H9-2	2
Q8N9H9-3	3
Q8N9H9-4	4

RefSeq proteins (2): NP_001164225, NP_001353156 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027956	CIROZ	Family
IPR049521	CIROZ_b	Domain

Pfam: PF15094

UniProt features (19 total): sequence variant 6, region of interest 4, splice variant 3, sequence conflict 2, compositionally biased region 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9H9-F1	53.62	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): GOBP_SPECIFICATION_OF_SYMMETRY, chr1p36, LMTK3_TARGET_GENES, ZNF22_TARGET_GENES, GSE10856_CTRL_VS_TNFRSF6B_IN_MACROPHAGE_UP, MIR647, HP_INGUINAL_HERNIA, HP_HYDROCELE_TESTIS, HP_HORSESHOE_KIDNEY, HP_ABNORMAL_PALATE_MORPHOLOGY, HP_HIGH_PALATE, HP_RETROGNATHIA, HP_ABNORMALITY_OF_THE_OUTER_EAR, HP_POSTERIORLY_ROTATED_EARS, HP_ABNORMAL_NASAL_BRIDGE_MORPHOLOGY

GO Biological Process (1): establishment of left/right asymmetry (GO:0061966)

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
determination of left/right symmetry	1
cellular anatomical structure	1

Protein interactions and networks

STRING

222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIROZ	OR5A1	Q8NGJ0	465
CIROZ	UBIAD1	Q9Y5Z9	399
CIROZ	ZNF347	Q96SE7	396
CIROZ	C6orf141	Q5SZD1	394
CIROZ	TMEM276	P0DTL5	384
CIROZ	RFPL2	O75678	371
CIROZ	IQSEC3	Q9UPP2	370
CIROZ	TAPT1	Q6NXT6	363
CIROZ	SMTNL2	Q2TAL5	359
CIROZ	GIPC2	Q8TF65	357
CIROZ	TANC1	Q9C0D5	354
CIROZ	IGSF21	Q96ID5	353
CIROZ	WDR70	Q9NW82	348
CIROZ	ANGPTL7	O43827	348
CIROZ	MYOZ3	Q8TDC0	340

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CIROZ	CCT3	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A1B0GV85, A1KXC4, A6QLF8, B1ARY8, O14594, O35188, O55145, O60279, O60667, O95196, P07141, P09603, P40225, P40226, P42705, P55066, P55067, P70628, P78423, Q149B8, Q17R60, Q28645, Q2LA85, Q2TB54, Q3TNW5, Q52S86, Q58Y74, Q5IS41, Q5M871, Q5R770, Q5T2D2, Q6PIX9, Q6UXF1, Q6ZVL6, Q7Z434, Q80XH2, Q8BHE4, Q8BT18, Q8C0D9, Q8CAE9

Diamond homologs: A0A8J1K1A4, B1ARY8, Q8N9H9, X1WBN4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	10
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3602007	NM_001170754.2(CIROZ):c.577C>T (p.Arg193Ter)	Pathogenic
3602008	NM_001170754.2(CIROZ):c.1210del (p.Gln404fs)	Pathogenic
4813836	NM_001170754.2(CIROZ):c.384C>A (p.Tyr128Ter)	Likely pathogenic

SpliceAI

2110 predictions. Top by Δscore:

Variant	Effect	Δscore
1:10948851:C:CT	acceptor_gain	1.0000
1:10948852:A:T	acceptor_gain	1.0000
1:10954985:CTCA:C	donor_loss	1.0000
1:10954986:TCACC:T	donor_loss	1.0000
1:10954987:CACC:C	donor_loss	1.0000
1:10955182:TGACA:T	acceptor_gain	1.0000
1:10955187:C:CC	acceptor_gain	1.0000
1:10957751:AGTC:A	acceptor_loss	1.0000
1:10957752:GTCTG:G	acceptor_loss	1.0000
1:10957753:TC:T	acceptor_loss	1.0000
1:10957754:C:CC	acceptor_gain	1.0000
1:10957754:C:T	acceptor_loss	1.0000
1:10957755:T:G	acceptor_loss	1.0000
1:10966357:CCT:C	donor_gain	1.0000
1:10948851:C:T	acceptor_gain	0.9900
1:10949568:TGGGG:T	donor_gain	0.9900
1:10954143:C:CC	acceptor_gain	0.9900
1:10954982:ATACT:A	donor_loss	0.9900
1:10954988:A:AC	donor_gain	0.9900
1:10954989:C:CC	donor_gain	0.9900
1:10955185:CA:C	acceptor_gain	0.9900
1:10955185:CACTG:C	acceptor_loss	0.9900
1:10955186:ACT:A	acceptor_loss	0.9900
1:10955187:C:G	acceptor_loss	0.9900
1:10957749:GGAGT:G	acceptor_gain	0.9900
1:10957750:GAGT:G	acceptor_gain	0.9900
1:10957752:GT:G	acceptor_gain	0.9900
1:10964296:A:C	acceptor_gain	0.9900
1:10966353:CCCA:C	donor_loss	0.9900
1:10966354:CCA:C	donor_loss	0.9900

AlphaMissense

5206 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000054692 (1:10975341 G>A,T), RS1000184126 (1:10960337 G>A), RS1000211439 (1:10956539 C>A), RS1000272318 (1:10954838 C>T), RS1000368192 (1:10950770 A>C), RS1000373500 (1:10983752 C>A,G,T), RS1000377643 (1:10980607 A>G), RS1000547814 (1:10961550 G>A,T), RS1000577702 (1:10970989 A>T), RS1000685894 (1:10946508 G>A), RS1000697559 (1:10965827 A>G), RS1000835367 (1:10979172 A>G), RS1000928323 (1:10978888 AG>A), RS1001033241 (1:10971364 G>A), RS1001057488 (1:10976975 T>C)

Disease associations

OMIM: gene MIM:619700 | disease phenotypes: MIM:621080

GenCC curated gene-disease

Disease	Classification	Inheritance
visceral heterotaxy	Limited	Autosomal recessive

Mondo (2): heterotaxy, visceral, 14, autosomal (MONDO:0976135), visceral heterotaxy (MONDO:0018677)

Orphanet (0):

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000034	Hydrocele testis
HP:0000085	Horseshoe kidney
HP:0000126	Hydronephrosis
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000476	Cystic hygroma
HP:0000494	Downslanted palpebral fissures
HP:0000767	Pectus excavatum
HP:0000822	Hypertension
HP:0000961	Cyanosis
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001651	Dextrocardia
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001746	Asplenia
HP:0001747	Accessory spleen
HP:0001748	Polysplenia
HP:0002099	Asthma
HP:0002205	Recurrent respiratory infections
HP:0002566	Intestinal malrotation
HP:0002780	Bronchomalacia
HP:0003363	Abdominal situs inversus

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003475_1	Beard thickness	4.000000e-07
GCST003983_5	Male-pattern baldness	3.000000e-27
GCST006095_5	Excessive hairiness	3.000000e-06
GCST006661_235	Male-pattern baldness	6.000000e-55
GCST006988_203	Blond vs. brown/black hair color	7.000000e-36

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
propionaldehyde	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, decreases expression	1
Methapyrilene	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01591928	Not specified	COMPLETED	Heterotaxy Syndrome and Intestinal Rotation Abnormalities - A Prospective Study
NCT01929967	Not specified	COMPLETED	Defining Immunodeficiency in Heterotaxy Syndrome: Pilot Study Data
NCT02432079	Not specified	RECRUITING	Molecular Genetics of Heterotaxy and Related Congenital Heart Defects