CFAP126

Summary

CFAP126 (cilia and flagella associated protein 126, HGNC:32325) is a protein-coding gene on chromosome 1q23.3, encoding Protein Flattop (Q5VTH2). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme.

Predicted to be involved in cilium organization and flagellated sperm motility. Located in several cellular components, including axonemal microtubule; cytosol; and plasma membrane.

Source: NCBI Gene 257177 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total — 4 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_001013625

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32325
Approved symbol	CFAP126
Name	cilia and flagella associated protein 126
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	Flattop, Fltp
Ensembl gene	ENSG00000188931
Ensembl biotype	protein_coding
OMIM	616119
Entrez	257177

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000367974, ENST00000906331

RefSeq mRNA: 1 — MANE Select: NM_001013625 NM_001013625

CCDS: CCDS30921

Canonical transcript exons

ENST00000367974 — 5 exons

Exon	Start	End
ENSE00001366543	161365526	161365702
ENSE00001369242	161366439	161366501
ENSE00001382476	161366198	161366278
ENSE00001383375	161364733	161365150
ENSE00001446033	161367842	161367876

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 99.07.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3171 / max 173.2433, expressed in 220 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15638	1.3171	220

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.07	gold quality
bronchial epithelial cell	CL:0002328	98.73	gold quality
bronchus	UBERON:0002185	97.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.83	gold quality
oviduct epithelium	UBERON:0004804	94.15	gold quality
fallopian tube	UBERON:0003889	92.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.27	gold quality
gastrocnemius	UBERON:0001388	91.72	gold quality
muscle of leg	UBERON:0001383	91.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.43	gold quality
nasal cavity epithelium	UBERON:0005384	89.75	gold quality
hypothalamus	UBERON:0001898	88.61	gold quality
anterior cingulate cortex	UBERON:0009835	88.22	gold quality
spinal cord	UBERON:0002240	88.05	gold quality
left testis	UBERON:0004533	87.80	gold quality
islet of Langerhans	UBERON:0000006	87.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.87	gold quality
nucleus accumbens	UBERON:0001882	86.51	gold quality
amygdala	UBERON:0001876	86.46	gold quality
right testis	UBERON:0004534	86.33	gold quality
epithelium of nasopharynx	UBERON:0001951	86.31	gold quality
right frontal lobe	UBERON:0002810	86.11	gold quality
caudate nucleus	UBERON:0001873	86.08	gold quality
smooth muscle tissue	UBERON:0001135	85.89	gold quality
prefrontal cortex	UBERON:0000451	85.58	gold quality
testis	UBERON:0000473	84.98	gold quality
rectum	UBERON:0001052	84.65	gold quality
calcaneal tendon	UBERON:0003701	84.30	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1656.27
E-MTAB-9154	yes	1039.46
E-MTAB-10283	yes	880.30
E-MTAB-10485	yes	708.77
E-CURD-114	yes	62.44
E-HCAD-1	yes	28.73
E-MTAB-10287	yes	27.54
E-GEOD-130148	yes	12.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting CFAP126, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127

Literature-anchored findings (GeneRIF, showing 1)

• Diabetes and CFAP126 gene mutation; are they really linked together? (PMID:39165147)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap126	ENSDARG00000070868
mus_musculus	Cfap126	ENSMUSG00000026649
rattus_norvegicus	Cfap126	ENSRNOG00000034221
drosophila_melanogaster	CG3062	FBGN0025612

Protein

Protein identifiers

Protein Flattop — Q5VTH2 (reviewed: Q5VTH2)

Alternative names: Cilia- and flagella-associated protein 126

All UniProt accessions (1): Q5VTH2

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme. Acts as a regulator of cilium basal body docking and positioning in mono- and multiciliated cells. Regulates basal body docking and cilia formation in multiciliated lung cells. Regulates kinocilium positioning and stereocilia bundle morphogenesis in the inner ear.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with DLG3.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Cell projection. Cilium. Apical cell membrane. Cilium axoneme. Flagellum axoneme.

Tissue specificity. Expressed in airway epithelial cells.

Similarity. Belongs to the Flattop family.

RefSeq proteins (1): NP_001013647* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038797	Fltp	Family

Pfam: PF22611

UniProt features (5 total): compositionally biased region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTH2-F1	73.17	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_CYTOPLASMIC_REGION, GOCC_APICAL_PART_OF_CELL, GOCC_MOTILE_CILIUM, GOCC_PLASMA_MEMBRANE_REGION, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, GOCC_CILIARY_BASAL_BODY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (3): flagellated sperm motility (GO:0030317), cilium organization (GO:0044782), cell projection organization (GO:0030030)

GO Molecular Function (0):

GO Cellular Component (15): cytosol (GO:0005829), axonemal microtubule (GO:0005879), plasma membrane (GO:0005886), cilium (GO:0005929), apical plasma membrane (GO:0016324), ciliary basal body (GO:0036064), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), axonemal B tubule inner sheath (GO:0160112), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cilium	2
sperm flagellum	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
organelle organization	1
plasma membrane bounded cell projection organization	1
cellular component organization	1
cytoplasm	1
cytoplasmic microtubule	1
axoneme	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
apical part of cell	1
plasma membrane region	1
microtubule organizing center	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP126	ST8SIA1	Q92185	670
CFAP126	UCN3	Q969E3	592
CFAP126	SPAG8	Q99932	474
CFAP126	NKX6-1	P78426	447
CFAP126	SDHC	Q99643	443
CFAP126	HOATZ	Q6PI97	431
CFAP126	SLC2A2	P11168	369
CFAP126	INTU	Q9ULD6	356
CFAP126	ANKRD66	B4E2M5	356
CFAP126	CD9	P21926	356
CFAP126	DYNLRB2	Q8TF09	353
CFAP126	NKAPD1	Q6ZUT1	348
CFAP126	NKX6-2	Q9C056	348
CFAP126	STOML3	Q8TAV4	340
CFAP126	AK8	Q96MA6	338

IntAct

0 interactions, top by confidence:

BioGRID (1): CFAP126 (Positive Genetic)

ESM2 similar proteins: A0A023PZL7, A1U7J5, C0HM83, O13913, O29691, O29755, O55755, O66406, O70889, P04016, P06424, P0C5Q0, P0DTB4, P11263, P12761, P13971, P14588, P16842, P20969, P23691, P40461, P92521, P93315, Q02247, Q08588, Q10261, Q197F7, Q2HJA2, Q32M92, Q3IK54, Q3SY05, Q54BB3, Q5T5A4, Q5VTH2, Q6B0X1, Q6B2I9, Q6CQE5, Q6GZT2, Q84295, Q8C5S3

Diamond homologs: A7RR34, B9ELP3, Q0P4F6, Q3KPS4, Q3SZT6, Q5VTH2, Q6P8X9, Q9W4I5, A8IVJ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1328459	GRCh37/hg19 1q23.3(chr1:161279433-161385237)x1	Pathogenic
1706512	GRCh37/hg19 1q23.3(chr1:161224742-161429290)x3	Pathogenic
619725	NM_003001.3(SDHC):c.406-408_*4225del	Pathogenic
7243	NC_000001.11:g.161367196_161370200delinsGTCA	Pathogenic
1527337	GRCh37/hg19 1q23.3(chr1:161207984-161404272)	Likely pathogenic
1710509	GRCh37/hg19 1q23.3(chr1:161216755-161409359)x3	Likely pathogenic
3062369	GRCh37/hg19 1q23.3(chr1:161224742-161415981)x3	Likely pathogenic

SpliceAI

418 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161366502:C:CC	acceptor_gain	1.0000
1:161367837:CTTA:C	donor_loss	1.0000
1:161367838:TTACC:T	donor_loss	1.0000
1:161367839:TAC:T	donor_loss	1.0000
1:161367841:C:CA	donor_loss	1.0000
1:161365524:ACCTT:A	donor_loss	0.9900
1:161365529:G:A	donor_gain	0.9900
1:161365698:TTTGC:T	acceptor_gain	0.9900
1:161365699:TTGC:T	acceptor_gain	0.9900
1:161365700:TGC:T	acceptor_gain	0.9900
1:161365701:GCC:G	acceptor_loss	0.9900
1:161365703:C:CC	acceptor_gain	0.9900
1:161366284:G:GC	acceptor_gain	0.9900
1:161366287:C:CT	acceptor_gain	0.9900
1:161366288:A:T	acceptor_gain	0.9900
1:161366440:T:TA	donor_gain	0.9900
1:161366498:CATA:C	acceptor_gain	0.9900
1:161366500:TA:T	acceptor_gain	0.9900
1:161367840:A:AC	donor_gain	0.9900
1:161367841:C:CC	donor_gain	0.9900
1:161365146:TGGGG:T	acceptor_gain	0.9800
1:161365151:C:CC	acceptor_gain	0.9800
1:161365701:GC:G	acceptor_gain	0.9800
1:161365702:CC:C	acceptor_gain	0.9800
1:161365709:A:C	acceptor_gain	0.9800
1:161366192:TCTCA:T	donor_loss	0.9800
1:161366193:CTCA:C	donor_loss	0.9800
1:161366194:TCA:T	donor_loss	0.9800
1:161366195:CA:C	donor_loss	0.9800
1:161366196:ACC:A	donor_loss	0.9800

AlphaMissense

1146 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161366487:G:C	F14L	0.983
1:161366487:G:T	F14L	0.983
1:161366489:A:G	F14L	0.983
1:161365682:G:C	F64L	0.980
1:161365682:G:T	F64L	0.980
1:161365684:A:G	F64L	0.980
1:161365693:A:G	W61R	0.978
1:161365693:A:T	W61R	0.978
1:161365672:A:G	W68R	0.976
1:161365672:A:T	W68R	0.976
1:161366229:C:T	G47D	0.970
1:161366241:G:T	A43D	0.969
1:161365624:G:T	R84S	0.968
1:161365670:C:A	W68C	0.967
1:161365670:C:G	W68C	0.967
1:161366229:C:A	G47V	0.964
1:161365623:C:G	R84P	0.960
1:161366230:C:G	G47R	0.960
1:161365691:C:A	W61C	0.956
1:161365691:C:G	W61C	0.956
1:161366465:A:G	W22R	0.954
1:161366465:A:T	W22R	0.954
1:161366232:C:G	R46P	0.953
1:161366226:T:G	H48P	0.948
1:161366223:A:G	L49P	0.945
1:161366227:G:C	H48D	0.944
1:161366242:C:G	A43P	0.943
1:161365665:A:G	M70T	0.942
1:161367864:G:T	A2D	0.940
1:161366223:A:T	L49Q	0.939

dbSNP variants (sampled 300 via entrez): RS1000398132 (1:161369334 C>T), RS1000682670 (1:161368379 A>G), RS1000708596 (1:161368096 C>A,T), RS1002666896 (1:161367424 A>C,G), RS1002716609 (1:161365429 C>A,G), RS1003654724 (1:161369717 A>G), RS1003732651 (1:161365531 C>G,T), RS1004346553 (1:161368853 A>C,G), RS1004420126 (1:161368500 A>T), RS1005157094 (1:161367533 T>G), RS1005209627 (1:161367266 G>A), RS1006591948 (1:161367054 C>T), RS1007035822 (1:161366727 A>T), RS1007180426 (1:161364774 T>A), RS1007190163 (1:161364425 C>G,T)

Disease associations

OMIM: gene MIM:616119 | disease phenotypes: MIM:605373

GenCC curated gene-disease

Mondo (1): pheochromocytoma/paraganglioma syndrome 3 (MONDO:0011544)

Orphanet (1): Hereditary pheochromocytoma-paraganglioma (Orphanet:29072)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565335	Paragangliomas 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
bisphenol A	affects expression	1
mancozeb	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Demecolcine	increases expression	1
Diethylstilbestrol	decreases expression	1
Lead	affects expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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